PMID:  Toxics. 2022 Aug 28 ;10(9). Epub 2022 Aug 28. PMID: 36136470 Abstract Title:  e-Cigarette Vapour Condensate Reduces Viability and Impairs Function of Human Osteoblasts, in Part, via a Nicotine Dependent Mechanism. Abstract:  Cigarette consumption negatively impacts bone quality and is a risk-factor for the development of multiple bone associated disorders, due to the highly vascularised structure of bone being exposed to systemic factors. However, the impact on bone to electronic cigarette (e-cigarette) use, which contains high doses of nicotine and other compounds including flavouring chemicals, metal particulates and carbonyls, is poorly understood. Here, we present the first evidence demonstrating the impact of e-cigarette vapour condensate (replicating changes in e-cigarette liquid chemical structure that occur upon device usage), on human primary osteoblast viability and function. 24 h exposure of osteoblasts to e-cigarette vapour condensate, generated from either second or third generation devices, significantly reduced osteoblast viability in a dose dependent manner, with condensate generated from the more powerful third generation device having greater toxicity. This effect was mediated in-part by nicotine, since exposure to nicotine-free condensate of an equal concentration had a less toxic effect. The detrimental effect of e-cigarette vapour condensate on osteoblast viability was rescued by co-treatment with the antioxidant N-Acetyl-L-cysteine (NAC), indicating toxicity may also be driven by reactive species generated upon device usage. Finally, non-toxic doses of either second or third generation condensate significantly blunted osteoblast osteoprotegerin secretion after 24 h, which was sustained for up to 7 days. In summary we demonstrate that e-cigarette vapour condensate, generated from commonly used second and third generation devices, can significantly reduce osteoblast viability and impair osteoblast function, at physiologically relevant doses. These data highlight the need for further investigation to inform users of the potential risks of e-cigarette use on bone health, including, accelerating bone associated disease progression, impacting skeletal development in younger users and to advise patients following orthopaedic surgery, dental surgery, or injury to maximise bone healing.

read more

PMID:  Ecotoxicol Environ Saf. 2023 May ;256:114867. Epub 2023 Apr 5. PMID: 37027940 Abstract Title:  Urinary bisphenol A and S are associated with diminished ovarian reserve in women from an infertility clinic in Northern China. Abstract:  Bisphenol A (BPA) has been demonstrated to cause ovarian toxicity including disruption of steroidogenesis and inhibition of follicle growth. Still, human evidence is lacking on its analogs such as bisphenol F (BPF) and bisphenol S (BPS). In this study, we aimed to investigate the associations between exposure to BPA, BPF, and BPS with ovarian reserve in women of childbearing age. We recruited 111 women from an infertility clinic in Shenyang, North China between September 2020 and February 2021. Anti-mllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) were measured as indicators of ovarian reserve. Urinary BPA, BPF, and BPS concentrations were quantified by ultra-high-performance liquid chromatography-triple quadruple mass spectrometry (UHPLC-MS/MS). Linear and logistic regression models were applied to assess the associations between urinary BPA, BPF, and BPS levels and indicators of ovarian reserve and DOR, respectively. Restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. Our results showed that urinary BPS concentrations were negatively associated with AMH ( = - 0.287, 95 %CI: - 0.505, - 0.070, P = 0.010) and this inverse relationship was further confirmed in the RCS model. In addition, higher levels of BPA and BPS exposure were associated with increased DOR risk (BPA: OR = 7.112, 95 %CI: 1.247, 40.588, P = 0.027; BPS: OR = 6.851, 95 %CI: 1.241, 37.818, P = 0.027). No significant associations of BPF exposure with ovarian reserve. Our findings implied that higher BPA and BPS exposure may be related to decreased ovarian reserve.

read more

PMID:  Sci Total Environ. 2023 Jul 1 ;880:163354. Epub 2023 Apr 5. PMID: 37023811 Abstract Title:  Trimester-specific associations of maternal exposure to bisphenols with neonatal thyroid stimulating hormone levels: A birth cohort study. Abstract:  BACKGROUND: Growing evidence suggests that exposure to bisphenol A (BPA) during pregnancy could interfere with neonatal thyroid function. Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as the substitutes of BPA. However, little is known about the effects of maternal exposure to BPS and BPF on neonatal thyroid function. The current study was aimed to investigate the trimester-specific associations of maternal exposure to BPA, BPS, and BPF with neonatal thyroid stimulating hormone (TSH) levels.METHODS: Between November 2013 and March 2015, a total of 904 mother-newborn pairs were recruited from the Wuhan Healthy Baby Cohort Study, providing maternal urine samples in the first, second, and third trimesters for bisphenol exposure assessment, and neonatal heel prick blood samples for TSH measurement. Multiple informant model and quantile g-computation were used to evaluate the trimester-specific associations of bisphenols individually and mixture with TSH, respectively.RESULTS: Each doubling concentration increase of maternal urinary BPA in the first trimester was significantly related to a 3.64 % (95% CI: 0.84 %, 6.51 %) increment in neonatal TSH. Each doubling concentration increase of BPS in the first, second and third trimesters were associated with 5.81 % (95 % CI: 2.27 %, 9.46 %), 5.70 % (95 % CI: 1.99 %, 9.55 %), 4.36 % (95 % CI: 0.75 %, 8.11 %) higher neonatal blood TSH, respectively. No significant association between trimester-specific BPF concentration and TSH was observed. The relationships between exposures to BPA/BPS and neonatal TSH were more evident in female infants. Quantile g-computation indicated that maternal co-exposure to bisphenols in the first trimester was significantly associated with neonatal TSH levels in a non-linear fashion.CONCLUSION: Maternal exposure to BPA and BPS were positively associated with neonatal TSH levels. The results indicated the endocrine disrupting effect of prenatal exposure to BPS and BPA, which should be of particular concern.

read more

PMID:  J Pineal Res. 2023 Mar 31:e12869. Epub 2023 Mar 31. PMID: 37002642 Abstract Title:  BPS-induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT-1/Nrf2/NFB and IR/PI3K/pAkt/GLUT-4 expressions in adult golden hamster. Abstract:  Ever-increasing occurrence of plastic-manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a "safer" replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS-induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3mg/kg BW i.p. alternate days) and BPS (150mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo-pituitary-ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ER, TR, and MT-1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript-1 (SIRT-1), forkhead box O-1 (FOXO-1), nuclear factor E2-related factor-2 (Nrf2), and phosphoinositide 3-kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa-B (NFB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor(TNF), C-reactive protein (CRP) and nitrite-nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter-4 (GLUT-4), connexin-43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental...

PMID:  PLoS One. 2023 ;18(3):e0283444. Epub 2023 Mar 30. PMID: 36996235 Abstract Title:  Relation of urinary bisphenol concentration and diabetes or prediabetes in French adults: A cross-sectional study. Abstract:  BACKGROUND: International research has recently shown an association between exposure to bisphenol A (BPA) and the risk of diabetes, although limited results are available for exposure to bisphenol S (BPS) and bisphenol F (BPF). The aim of this study was to examine the relationships between impregnation with BPA, BPS, and BPF and the prevalence of diabetes or prediabetes in the French adult population.METHODS: Based on the Esteban cross-sectional study, 852 adults aged 18 to 74 years living in France were included. To assess the link between urinary concentration of BPA, BPS and BPF and a state of dysglycemia (diabetes or prediabetes), logistic regression multivariable models were performed and adjusted for known risk factors for diabetes and urine creatinine concentration.RESULTS: The percentage of included individuals with diabetes or prediabetes was 17.8% (95% CI = [15.3-20.4]). Urinary BPA concentration was significantly higher in people with diabetes or prediabetes, independent of the known risk factors for diabetes (OR for an increase of 0.1 units in log-transformed concentration of BPA (g/L) = 1.12; 95%CI = [1.05-1.19], p

read more

PMID:  J Hazard Mater. 2023 Jun 15 ;452:131288. Epub 2023 Mar 24. PMID: 36989771 Abstract Title:  Low-dose BPA and its substitute BPS promote ovarian cancer cell stemness via a non-canonical PINK1/p53 mitophagic signaling. Abstract:  The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013-2016 data. We treated human ovarian cancer cells with 0-1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.

read more

PMID:  Toxicol Ind Health. 2023 May ;39(5):237-247. Epub 2023 Mar 23. PMID: 36951826 Abstract Title:  Postnatal exposure to Bisphenol S induces liver injury in mice: Possible implication of PPARreceptor. Abstract:  There is considerable evidence that Bisphenol S (BPS) induces various toxicological effects and is an industrial health issue. However, little data are available on the in vivo effects of BPS on the liver, a major target of drug toxicity. In this study, we evaluated the potential harmfulness of low levels of BPS in the liver of male mice. Also, we investigated the interaction between BPS and peroxisome proliferator-activated receptor-gamma (PPAR) by computational docking approach. PPARis a member of the superfamily of nuclear hormone receptors. It acts as a transcription factor and regulates the genes involved in lipid and glucose metabolism and in inflammation and necrosis. Mice were exposed to BPS, in drinking water at 25, 50, and 100 g/kg for 10 weeks. The protocol was started after weaning. At the time of sacrifice, blood samples were collected for a biochemical analysis, followed by liver tissue collection for histopathological study. Results showed that BPS-induced hypertriglyceridemia, increased liver injury markers, and initiated histopathological changes, including inflammatory cell infiltration, hepatocellular necrosis, and steatosis. BPS did not affect glycated hemoglobin (HbA1C). Interestingly, data showed that BPS could interact with the PPARligand-binding pocket by hydrogen bonds with Asn 219, Cys 276, Ser 280, and Thr 283. We suggest that PPARis among the targets of BPS and could play a key role in the cascade reaction of BPS-induced liver disruption. These findings support the hypothesis that the post-weaning period is sensitive to low-dose BPS exposure that can lead to dyslipidemia signature later in life.

read more

PMID:  Toxicology. 2023 Jun 1 ;491:153513. Epub 2023 Apr 17. PMID: 37075930 Abstract Title:  Polystyrene microplastics aggravate acute pancreatitis in mice. Abstract:  Microplastics (MPs) with a diameter of

read more

PMID:  Eur Rev Med Pharmacol Sci. 2023 Apr ;27(7):2888-2898. PMID: 37070889 Abstract Title:  Urine phthalate levels were associated with skin barrier dysfunction and atopic sensitization in children. Abstract:  OBJECTIVE: Phthalates can cause immunological disorders and aggravate allergic diseases. Thus, we investigated the relationship between urinary phthalate, skin barrier function, and atopic sensitization in children.PATIENTS AND METHODS: In total, 448 school children [334 with severe allergic disease; and 123 with severe atopic dermatitis (AD)] aged 10-12 years were enrolled in this study between June and July 2017. Four high-molecular-weight phthalates (HMWP) [4HMWP] and three low-molecular-weight phthalates (LMWP) [3LMWP] metabolites in urine samples, specific immunoglobulin E (IgE), and total eosinophil count were measured. Four-part trans epidermal water loss (TEWL) (cheek, leg, and upper/lower arm;4TEWL) was measured to evaluate the skin barrier function.RESULTS: After adjusting for confounding variables,4TEWL was significantly associated with the quartiles of urinary4HMWP [adjusted=7.897, 95% confidence interval (CI): 0.636-15.158, p=0.033] and3LMWP (adjusted=9.670, 95% CI: 2.422-16.919, p=0.009). The adjusted analyses revealed that the quartiles of urinary4HMWP and3LMWP were not significantly associated with total eosinophil count, atopic sensitization, and severe AD (p>0.05). According to the quartiles of urinary4HMWP and3LMWP, there were significant differences in the TEWL of the lower arm and leg (p

read more

PMID:  Environ Toxicol. 2023 Jul ;38(7):1628-1640. Epub 2023 Mar 29. PMID: 36988346 Abstract Title:  Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway. Abstract:  Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500mg/kg/d) for 8weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200M) for 24h. About 50M DAPT and 100g/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

read more

PMID:  Antibiotics (Basel). 2023 Feb 24 ;12(3). Epub 2023 Feb 24. PMID: 36978330 Abstract Title:  Extract as a Promising Antimicrobial and Antivirulence Therapy. Abstract:  The worldwide crises from multi-drug-resistant (MDR) bacterial infections are pushing us to search for new alternative therapies. The renewed interest in medicinal plants has gained the attention of our research group.L. () is one of the traditional medicines used for a wide range of diseases. Therefore, we evaluated the antimicrobial activities of ethanolic extract ofThe inhibitions zones, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and fractional inhibitor concentration indices (FICI) against Gram+ve and -ve pathogens were detected. The bioactive compounds fromextract were identified by mass spectroscopy, thin-layer chromatography, and bio-autographic assay. We performed scanning electron microscopy (SEM) and molecular docking studies to confirm possible mechanisms of actions and antivirulence activities, respectively. We found more promising antimicrobial activities against MDR pathogens with MIC and MBC values for() and(), i.e., (0.78, 3.12 mg/mL) and (1.56, 3.12 mg/mL), respectively. The antimicrobial activities of this extract were attributed to its capability to impair cell membrane permeability, inducing bacterial cell lysis, which was confirmed by the morphological changes observed under SEM. The synergistic interactions between this extract and commonly used antibiotics were confirmed (FICI values

read more

PMID:  Int J Environ Health Res. 2023 Mar 27:1-16. Epub 2023 Mar 27. PMID: 36973994 Abstract Title:  Association between phthalates and sleep problems in the U.S. adult females from NHANES 2011-2014. Abstract:  There is little research on the relationship between phthalates exposure and sleep problems in adult females, with existing studies only assessing the association between exposure to individual phthalates with sleep problems.We aimed to analyse the relationship between phthalates and sleep problems in 1366 US females aged 20 years and older from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) by age stratification. Multivariate logistic regression showed that the fourth quartile of MECPP increased the risk of sleep problems in females aged 20-39 compared with the reference quartile (OR: 1.87, 95% CI: 1.14, 3.08). The WQS index was significantly associated with the sleep problems in females aged 20-39. In the BKMR, a positive overall trend between the mixture and sleep problems in females aged 20-39. In this study, we concluded that phthalates might increase the risk of sleep problems in females aged 20-39.

read more

PMID:  J Expo Sci Environ Epidemiol. 2023 Mar 23. Epub 2023 Mar 23. PMID: 36959356 Abstract Title:  Individual and joint effects of phthalates exposure on the risk of early miscarriage. Abstract:  BACKGROUND: The exposure levels of phthalates in humans have dropped dramatically. Little is known about the individual and joint effects of phthalates exposure at low levels on the risk of early miscarriage.OBJECTIVE: To examine the association between exposure to phthalates individually or as a mixture and early miscarriage.METHODS: A case-control study was conducted in Shanghai, China during 2019-2020. A total of 291 women seeking medical services due to miscarriage (cases) and 308 women planning to terminate an unintended pregnancy (controls) within 12 gestational weeks were recruited. Urinary concentrations of eight phthalate metabolites were determined by ultra-performance liquid chromatography. We included 534 women in the main analysis who had available data on both phthalates exposure and complete information on potential confounders. We used logistic regression and Bayesian kernel machine regression (BKMR) to examine the associations of concentrations of phthalates with miscarriage.RESULTS: Among the phthalate metabolites, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) had the highest concentration (8.10ng/mL), followed by mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, 2.68ng/mL) and monobutyl phthalate (MBP, 2.24ng/mL). Higher concentrations of MBP, mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP and the molar sum of di(2-ethylhexyl) phthalate (DEHP) metabolites (DEHPm) were associated with an increased risk of miscarriage exhibiting a dose-response relationship. The most evident association of miscarriage was found withDEHPm, with adjusted odds ratio (95% confidence interval) of 1.94 (1.14, 3.31) for the second quartile, 2.83 (1.67, 4.79) for the third quartile and 4.28 (2.49, 7.37) for the fourth quartile compared to the first quartile. Consistently, the phthalate mixture was positively associated with the risk of miscarriage and DEHP was the predominant contributor to the joint effect in BKMR model.IMPACT: Phthalates are a family of synthetic chemicals mainly used as plasticizers, solvents and additives in a large variety of industrial and consumer products, including food packing materials, toys, gloves, medical devices and personal care products. Although exposure levels of phthalates of pregnant women have declined sharply over the past few decades, phthalates exposure was still associated with an increased risk of early miscarriage. Our findings suggest that future researchers and policy makers might need to take low-dose effects of phthalates into account regarding the reproductive toxicity of phthalates exposure in humans.SIGNIFICANCE: Our findings contribute to the awa...

PMID:  Environ Pollut. 2023 Jun 1 ;326:121462. Epub 2023 Mar 21. PMID: 36958664 Abstract Title:  Oxidative stress mediates the associations between phthalate exposures and thyroid cancer/benign nodule risk. Abstract:  Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F(8-isoPGF)]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values

read more

PMID:  Sci Total Environ. 2023 Jun 20 ;878:162741. Epub 2023 Mar 11. PMID: 36914131 Abstract Title:  Persistent immunosuppressive effects of dibutyl phthalate exposure in adult male mice. Abstract:  Increased exposure to manmade chemicals may be linked to an increase in immune-related diseases in humans and immune system dysfunction in wildlife. Phthalates are a group of endocrine-disrupting chemicals (EDCs) suspected to influence the immune system. The aim of this study was to characterize the persistent effects on leukocytes in the blood and spleen, as well as plasma cytokine and growth factor levels, one week after the end of five weeks of oral treatment with dibutyl phthalate (DBP; 10 or 100 mg/kg/d) in adult male mice. Flow cytometry analysis of the blood revealed that DBP exposure decreased the total leukocyte count, classical monocyte and T helper (Th) populations, whereas it increased the non-classical monocyte population compared to the vehicle control (corn oil). Immunofluorescence analysis of the spleen showed increased CD11bLy6G(marker of polymorphonuclear myeloid-derived suppressor cells; PMN-MDSCs), and CD43staining (marker of non-classical monocytes), whereas CD3(marker of total T cells) and CD4(marker of Th cells) staining decreased. To investigate the mechanisms of action, levels of plasma cytokines and chemokines were measured using multiplexed immunoassays and other key factors were analyzed using western blotting. The observed increase in M-CSF levels and the activation of STAT3 may promote PMN-MDSC expansion and activity. Increased ARG1, NOX2 (gp91phox), and protein nitrotyrosine levels, as well as GCN2 and phosphor-eIRF, suggest that oxidative stress and lymphocyte arrest drive the lymphocyte suppression caused by PMN-MDSCs. The plasma levels of IL-21 (promotes the differentiation of Th cells) and MCP-1 (regulates migration and infiltration of monocytes/macrophages) also decreased. These findings show that adult DBP exposure can cause persistent immunosuppressive effects, which may increase susceptibility to infections, cancers, and immune diseases, and decrease vaccine efficacy.

read more

PMID:  Environ Res. 2023 May 15 ;225:115622. Epub 2023 Mar 7. PMID: 36894111 Abstract Title:  A cross sectional pilot study to assess the role of phthalates on respiratory morbidity among patients with chronic obstructive pulmonary disease. Abstract:  BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) affects16 million U.S. adults. Phthalates, synthetic chemicals in consumer products, may adversely impact pulmonary function and airway inflammation; however, their role on COPD morbidity remains unknown.OBJECTIVE: We examined associations between phthalate exposures and respiratory morbidity among 40 COPD patients who were former smokers.METHODS: We quantified 11 phthalate biomarkers in urine samples collected at baseline in a 9-month prospective cohort study in Baltimore, Maryland. COPD baseline morbidity measures included: health status and quality of life measures (CAT: COPD Assessment Test, CCQ: Clinical COPD Questionnaire, SGRQ: St. George's Respiratory Questionnaire; mMRC: Modified Medical Research Council Dyspnea Scale), and lung function. Information on prospective exacerbation data was monitored monthly during the 9-month longitudinal follow-up period. To examine associations between morbidity measures and phthalate exposures, we used multivariable linear and Poisson regression models for continuous and count outcomes, respectively, adjusting for age, sex, race/ethnicity, education, and smoking pack-years.RESULTS: Higher mono-n-butyl phthalate (MBP) concentrations were associated with increased CAT(, 2.41; 95%CI, 0.31-4.51), mMRC (, 0.33; 95%CI 0.11-0.55), and SGRQ (, 7.43; 95%CI 2.70-12.2) scores at baseline. Monobenzyl phthalate (MBzP) was also positively associated with CCQ and SGRQ scores at baseline. Higher concentrations of the molar sum of Di (2-ethylhexyl) phthalate (DEHP) were associated with increased incidence of exacerbations during the follow-up period (incidence rate ratio, IRR = 1.73; 95%CI 1.11, 2.70 and IRR = 1.94; 95%CI 1.22, 3.07, for moderate and severe exacerbations, respectively). MEP concentrations were inversely associated with incidence of exacerbations during the follow-up period.CONCLUSIONS: We found that exposure to select phthalates was associated with respiratory morbidity among COPD patients. Findings warrant further examination in larger studies given widespread phthalate exposures and potential implications for COPD patients should relationships observed be causal.

read more

PMID:  J Environ Sci Health A Tox Hazard Subst Environ Eng. 2023 ;58(1):81-90. Epub 2023 Feb 28. PMID: 36852734 Abstract Title:  Neuro-protective potentials of N-acetylcysteine and zinc against di(2-ethylhexyl)-phthalate-induced neuro-histopathology and dys-regulations of Dopamine and Glutamate in rat brain. Abstract:  This study examined neuro-protective potentials of N-acetyl-cysteine (NAC) and Zinc on expression levels of Dopamine and Glutamate in the Cerebrum, Hypothalami and Pituitary Glands in Di(2-ethylhexyl)-phthalate (DEHP)-induced neurotoxicity in rats. Thirty-six adult male Wistar rats were randomly divided into 6 groups (n=6). Group 1 was control. Groups 2-6 received oral administrations of 100mg/kg NAC, 0.5mg/kg Zinc, 750mg/kg DEHP, DEHP+NAC doses and DEHP+Zinc doses respectively for 21days. Brain histology (Heamatoxyline and Eosine technique), histochemical and enzyme-linked-immunosorbent assays of Dopamine and Glutamate in homogenates of Cerebrum, Hypothalami and Pituitary Glands were evaluated. Data were statistically analyzed using One-way-ANOVA with Tukey-post-hoc test at0.05. Histo-pathological evaluations of Cerebrum, Hypothalami and Pituitary Glands showed gross histo-alterations and neurodegenerative changes (Group 4), mild histo- and neuro-degenerative changes (Groups 5 and 6) and normal histology (Group 1). Histochemical analyses showed higher Dopamine levels in Hypothalami (Group 5) and Pituitary Glands (Groups 5 and 6), compared with Group 4. Furthermore, results showed lower Glutamate levels in Cerebrum, Hypothalami and Pituitary Glands of Groups 5 and 6, compared with Group 4. Overall, NAC and Zinc conferred neuro-protection and histo-protection against DEHP-induced neuro-toxicity, neuro-histopathology, decreased Dopamine levels and increased Glutamate levels.

read more

PMID:  Gynecol Endocrinol. 2023 Dec ;39(1):2189969. PMID: 37040789 Abstract Title:  -Acetyl-l-cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress. Abstract:  Gestational diabetes mellitus (GDM) affects 7% of pregnant women worldwide. How to effectively treat GDM has always been a concern of people.In this study, a diabetes model was established by drug-induced mice. Subsequently, the blood glucose levels and serum insulin changes of the mice after-acetyl-l-cysteine (NAC) treatment were observed. At the same time, the effect of NAC on reproduction of GDM mice was recorded.Mice fed NAC showed significantly improved glucose tolerance and insulin sensitivity compared to Diabetic/Control. Total serum cholesterol, serum triglycerides, and serum low-density lipoprotein were significantly reduced, and atherosclerosis index was much lower than in control mice. In addition, Diabetic/Control mice had lower litter sizes and higher birth weights. NAC treatment significantly restored litter size and reduced birth weight in Diabetic/Control mice. It was found in WB assay that the NAC-fed group significantly increased nuclear Nrf2 and HO-1 expression levels.NAC can improve blood glucose tolerance in GDM mice; NAC effectively relieves the symptoms of hyperlipidemia caused by GDM; NAC enhances the expression of Nrf2/HO-1 in the liver, thereby restoring redox homeostasis. NAC can reduce gestational diabetes-related disease indicators by oral administration, and has a beneficial effect on the offspring of pregnant mice (reduces its diabetes disease indicators).

read more

PMID:  Am J Sports Med. 2023 May ;51(6):1596-1607. Epub 2023 Apr 5. PMID: 37017249 Abstract Title:  The Effect of Vitamin C and-Acetylcysteine on Tendon-to-Bone Healing in a Rodent Model of Rotator Cuff Repair. Abstract:  BACKGROUND: Oxidative stress inhibits tendon-to-bone healing after rotator cuff repair. Regulation of oxidative stress has the potential to accelerate this healing, but its mechanism remains unclear.PURPOSE: To investigate the effects of reducing oxidative stress by applying antioxidants, such as-acetylcysteine (NAC) and vitamin C (VC), on rotator cuff repair in a rat rotator cuff repair model.STUDY DESIGN: Controlled laboratory study.METHODS: A total of 48 Sprague Dawley rats underwent bilateral surgery to repair the infraspinatus tendon to its insertion site 1 week after detachment. Rats were assigned to either the NAC group, the VC group, or a control group. Histological evaluation was performed via hematoxylin-eosin or toluidine blue staining, and oxidative stress was assessed via dihydroethidium intensity and protein carbonyl concentration at 3 and 6 weeks. Superoxide dismutase 1 (SOD1), SOD2, SOD3, peroxiredoxin 5, collagen type I (COL1), COL3, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 expression and SOD activity were determined at 3 and 6 weeks. Biomechanical tests were performed at 6 and 12 weeks.RESULTS: Histological evaluation showed that the number of chondrocytes in the NAC group at 6 weeks and in the VC group at 3 and 6 weeks, the area of fibrocartilage at 6 weeks in the VC group, and collagen fibers at 6 weeks in the NAC and VC groups were significantly increased compared with those in the control group. Dihydroethidium intensity at 3 and 6 weeks and protein carbonyls at 6 weeks in the NAC and VC groups were significantly decreased. SOD1 expression and SOD activity at 3 weeks in the VC group and peroxiredoxin 5 expression at 6 weeks in the NAC group were significantly upregulated compared with that in the control group. COL3 expression was significantly upregulated at 6 weeks in the VC group, and MMP-13 expression was significantly decreased at 6 weeks in the NAC and VC groups. The biomechanical strength showed no significant difference.CONCLUSION: Antioxidant treatment, via NAC or VC administration, reduced oxidative stress in the rotator cuff repair site and accelerated healing.CLINICAL RELEVANCE: These findings provide essential indications to develop clinical strategies for improved healing after rotator cuff surgical repair in patients.

read more

PMID:  Environ Res. 2023 Jan 15 ;217:114956. Epub 2022 Nov 26. PMID: 36442523 Abstract Title:  Environmental impacts of covid-19 pandemic: Release of microplastics, organic contaminants and trace metals from face masks under ambient environmental conditions. Abstract:  The covid-19 pandemic era was characterized by heavy usage and disposal of medical face masks, now estimated at over 1.24 trillion. Few studies had attempted to demonstrate the release of microplastics from face masks using simulated conditions and application of mechanical forces, far different from the effects experienced by face masks dumped in the open environment, in landfills and dumpsites. In the current study, we monitored the release of microplastics, organic contaminants and toxic metals from medical face masks degraded under normal outdoor environmental conditions, over a period of 60 weeks. We showed that face mask's decomposition proceeded via sunlight (UV) - initiated oxidative degradation, leading to the replacement of methylene (CH-) and alkyl (CH-) groups in face mask's polypropylene backbone with hydroxyl and ketonic functional groups. Organic compounds released from decaying face masks into the surrounding soil included alkanes, alkenes, carboxylic acids/diesters and phthalate esters. Mean maximum concentration of phthalates in the soil ranged from 3.14 mg/kg (diethyl phthalate) to 11.68 mg/kg di(2-ethylhexyl) phthalate. Heavy metals, including Cu, Pb, Cd, As, Sn and Fe, were released into the soil, leading to contamination factors of 3.11, 2.84, 2.42, 2.26, 1.80 and 0.99, respectively. Together, the metals gave a pollution load index (PLI) of 2.102, indicating that they constitute moderate pollution of the soil surrounding the heap of face masks. This study provides a realistic insight into the fate and impacts of the enormous amounts of face masks, disposed or abandoned in soil environments during the covid-19 pandemic.

read more

PMID:  Environ Pollut. 2023 Jan 1 ;316(Pt 2):120703. Epub 2022 Nov 17. PMID: 36403876 Abstract Title:  Dynamic variation and inhalation exposure of organophosphates esters and phthalic acid esters in face masks. Abstract:  The coronavirus pandemic (COVID-19) has posed a huge global health threat since December 2019. Wearing face masks is known as an effective measure for controlling the wide spread of COVID-19 and its variants. But on the other hand, face masks could be a potential source of organophosphate esters (OPEs) and phthalic acid esters (PAEs) as they are extensively added in masks. However, knowledge associated with the occurrence as well as inhalation risks of OPEs and PAEs in masks is limited. In this study, OPEs and PAEs were determined in different types of mask samples collected from the local market. OPEs and PAEs were detected in mask samples ranging from 36.7 to 855 ng/g, and from 251 to 3830 ng/g, respectively. Relatively lower OPEs and PAEs concentrations were observed in disposable mask for toddlers. Simulated inhalation experiment indicated that the mass loss of OPEs and PAEs was 136 and 3910 ng/mask in disposable masks, 71.9 and 763 ng/mask in disposable mask for toddlers, 924 and 1020 ng/mask in N95 mask after 12 h, respectively. Significantly negative correlations were exhibited between the decrement of OPEs in masks and the increment of OPEs in corresponding polyurethane foams (PUFs) during the course, elucidating OPEs released from masks could be well captured by PUFs. With regard to the variation over time, predominant OPE and PAE analogues showed semblable release and absorption tendency in mask and corresponding PUF. Inhalation exposure risk of OPEs and PAEs was estimated based on the increment of pollutants in PUF. The estimated daily intakes (EDIs), hazard index (HI) and carcinogenic risk (CR) were also calculated and they were within the threshold levels. This study provides the evidence of OPEs and PAEs releasing from the face masks during wearing and unveiled a potential source of OPEs and PAEs exposure to humans.

read more

PMID:  J Hazard Mater. 2022 Jan 15 ;422:126848. Epub 2021 Aug 6. PMID: 34403943 Abstract Title:  Face mask-A potential source of phthalate exposure for human. Abstract:  Face masks are necessary for fighting against the coronavirus disease 2019 around the world. As the face mask is usually made from polymers and phthalates are widely-used additives into the polymers, the face mask could be a potential source of phthalate exposure to humans. However, limited knowledge is available on the occurrence and risks of the phthalates from the face mask. In this study, twelve phthalates were determined in 56 mask samples collected from different countries. The phthalates were detected in all the samples with total levels ranging from 115 ng/g to 37,700 ng/g. Estimated daily intakes (EDIs) of the phthalates from the masks ranged from 3.71 to 639 ng/kg-bw/day, and the EDIs of the phthalates from masks for toddlers were approximately 4-5 times higher than those for adults. Non-carcinogenic risks in relation to the phthalates in masks were found to be within safe levels, yet 89.3% of the mask samples exhibited potential carcinogenic effects to humans. The extent of the risks for wearing masks located at a moderate level comparing with other skin-contacted products. This study unveiled a potential source of phthalate exposure to human, and indicated necessity of managing types and levels of additives in the face masks.

read more

PMID:  Toxics. 2023 Jan 17 ;11(2). Epub 2023 Jan 17. PMID: 36850963 Abstract Title:  Face Mask: As a Source or Protector of Human Exposure to Microplastics and Phthalate Plasticizers? Abstract:  Wearing masks has become the norm during the Coronavirus disease pandemic. Masks can reportedly interface with air pollutants and release microplastics and plastic additives such as phthalates. In this study, an experimental device was set up to simulate the impact of five kinds of masks (activated-carbon, N95, surgical, cotton, and fashion masks) on the risk of humans inhaling microplastics and phthalates during wearing. The residual concentrations of seven major phthalates ranged from 296 to 72,049 ng/g (median: 1242 ng/g), with the lowest and the highest concentrations detected in surgical (median: 367 ng/g) and fashion masks (median: 37,386 ng/g), respectively. During the whole inhalation simulation process, fragmented and 20-100m microplastics accounted for the largest, with a rapid release during the first six hours. After one day's wearing, that of 6 h, while wearing different masks, 25-135 and 65-298 microplastics were inhaled indoors and outdoors, respectively. The total estimated daily intake of phthalates with indoor and outdoor conditions by inhalation and skin exposure ranged from 1.2 to 13 and 0.43 to 14 ng/kg bw/d, respectively. Overall, surgical masks yield a protective effect, while cotton and fashion masks increase human exposure to microplastics and phthalates both indoors and outdoors compared to no mask wearing. This study observed possible risks from common facemasks and provided suggestions to consumers for selecting suitable masks to reduce exposure risks from microplastics and phthalate acid.

read more

PMID:  BMC Microbiol. 2023 Apr 20 ;23(1):112. Epub 2023 Apr 20. PMID: 37081381 Abstract Title:  Antibacterial effect of vitamin C against uropathogenic E. coli in vitro and in vivo. Abstract:  BACKGROUND: Resistance to antibiotics has increased steadily over time, thus there is a pressing need for safer alternatives to antibiotics. Current study aims to evaluate the influence of vitamin C as an antibacterial and anti-biofilm agent against uropathogenic E. coli (UPEC) strains. The expression of beta-lactamases and biofilm encoding genes among E. coli isolates before and after treating the isolates with sub MIC of vitamin C was analyzed by Real-time PCR. The in vivo assessment of the antibacterial and anti-biofilm effects of vitamin C against uropathogenic E. coli strains was done using a urinary tract infection (UTI) rat model.RESULTS: The effective concentration of vitamin C that could inhibit the growth of most study isolates (70%) was 1.25 mg/ml. Vitamin C showed a synergistic effect with most of the studied antibiotics; no antagonistic effect was detected at all. Vitamin C showed an excellent anti-biofilm effect against studied isolates, where 43 biofilm-producing isolates were converted to non-biofilm at a concentration of 0.312 mg/ml. The expression levels of most studied genes were down-regulated after treatment of E. coli isolates with vitamin C. In vivo assessment of vitamin C in treating UTIs showed that vitamin C has a rapid curative effect as the comparable antibiotic. Administration of both vitamin C and nitrofurantoin at a lower dose for treatment of UTI in rats had a better effect.CONCLUSION: Vitamin C as an antibacterial and anti-biofilm agent either alone or in combination with antibiotics could markedly improve UTI in experimental rats.

read more

PMID:  Inflammopharmacology. 2023 Apr 18:1-6. Epub 2023 Apr 18. PMID: 37071316 Abstract Title:  The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials. Abstract:  BACKGROUND AND AIMS: Vitamin C appears to be a viable treatment option for patients with COVID-19.METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of vitamin C versus comparative interventions in patients with COVID-19. The outcome of interest was all-cause mortality.RESULTS: The meta-analysis of eleven trials using a random-effects model revealed significant reduction in the risk of all-cause mortality with the administration of vitamin C among patients with COVID-19 relative to no vitamin C (pooled odds ratio=0.53; 95% confidence interval 0.30-0.92). Subgroup analysis of studies that included patients with severe COVID-19 also produced findings of significant mortality reduction with the administration of vitamin C relative to no vitamin C (pooled odds ratio=0.47; 95% confidence interval 0.26-0.84).CONCLUSION: Overall, evidence from RCTs suggests a survival benefit for vitamin C in patients with severe COVID-19. However, we should await data from large-scale randomized trials to affirm its mortality benefits.

read more

PMID:  Int J Mol Sci. 2023 Apr 5 ;24(7). Epub 2023 Apr 5. PMID: 37047746 Abstract Title:  The Role of Vitamin C and Vitamin D in the Pathogenesis and Therapy of Periodontitis-Narrative Review. Abstract:  Periodontitis is a common disorder affecting the bone and soft tissues of the periodontal complex. When untreated, it may lead to severe mobility or even loss of teeth. The pathogenesis of periodontitis is complex, with crucial factors being chronic inflammation in gingival and periodontal tissues and oral microbiome alterations. However, recent studies highlight the alleged role of vitamins, such as vitamin C (VitC) and vitamin D (VitD), in the development of the disease. VitC regulates numerous biochemical reactions, but foremost, it is involved in synthesizing collagen. It was reported that VitC deficiency could lead to damage to the periodontal ligaments. VitC supplementation improves postoperative outcomes in patients with periodontitis. VitD is a steroid derivative that can be produced in the skin under ultraviolet radiation and later transformed into an active form in other tissues, such as the kidneys. VitD was established to decrease the expression of proinflammatory cytokines in gingiva and regulate the proper mineral density of teeth. Moreover, the supplementation of VitD was associated with better results in the nonsurgical treatment of periodontitis. In this review, we summarize recent knowledge on the role of vitamins C and D in the pathogenesis and treatment of periodontitis.

read more

PMID:  Eur Rev Med Pharmacol Sci. 2023 Mar ;27(6):2277-2287. PMID: 37013745 Abstract Title:  Elucidation of the role of-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice. Abstract:  OBJECTIVE: Although methotrexate (MTX) is used to treat several malignancies and chronic inflammatory diseases, its clinical use is constrained because of its negative side effects, the most prevalent of which are hepatotoxicity and nephrotoxicity. So, this study aims to determine whether-lipoic acid (ALA) and vitamin C can protect mice against the liver damage that methotrexate causes.MATERIALS AND METHODS: A total of 49 male mice were divided into seven groups at random. Group I received sodium bicarbonate, while groups II to VII received an intraperitoneal injection of MTX (20 mg/kg) on the tenth day, following ten days of pretreatment with ALA (60 mg/Kg), ALA (120 mg/Kg), vitamin C (100 mg/Kg), vitamin C (200 mg/Kg), ALA (60 mg/Kg), and vitamin C (100 mg/kg).RESULTS: When compared to mice in group I, mice in group II (the control group) had significantly higher levels of the enzymes malondialdehyde (MDA), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significantly lower (p

read more

PMID:  Food Sci Nutr. 2023 Apr ;11(4):1931-1939. Epub 2023 Jan 12. PMID: 37051351 Abstract Title:  Alleviative effects of-lipoic acid on muscle atrophy via the modulation of TNF-/JNK and PI3K/AKT pathways in high-fat diet and streptozotocin-induced type 2 diabetic rats. Abstract:  Diabetes mellitus (DM) is often accompanied by clinical complications such as sarcopenia. Previous studies have indicated that oxidative stress and insulin resistance (IR) are highly associated with the pathogenesis of diabetic myopathy.-lipoic acid (ALA), a potent biological antioxidant, exists abundantly in a variety of plants and vegetables. This study aimed to investigate the ameliorative effect of ALA on muscle atrophy in type 2 diabetic rats induced by high-fat diet feeding (HFD) plus streptozotocin (STZ) injection. The HFD/STZ-induced diabetic rats were orally administered 50, 100, or 200mg/kg body weight ALA once a day for 13weeks. The results showed that ALA at the tested concentrations significantly increased the soleus muscle mass and muscle fibers in diabetic rats. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-, were found to decrease in both the serum and muscle of ALA-treated diabetic rats. ALA significantly reduced the protein-expression levels of phosphorylated c-Jun N-terminal kinase (pJNK)/JNK, forkhead box O3 (FOXO3), and muscle ring-finger protein-1 (Murf1); whereas, it enhanced the protein-expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT)/AKT, myogenin determination gene D (MyoD), the mechanistic target of rapamycin (mTOR), and myosin heavy chain (MyHC) in the soleus muscle of diabetic rats. The results from this study suggested that ALA treatment may preserve soleus muscle mass, alleviate muscle atrophy by suppressing the TNF-/JNK pathway, and ameliorate the PI3K/AKT pathway in HFD/STZ-induced type 2 diabetic rats.

read more

Was the AIDS epidemic caused by natural processes? Or, were the experimental oral polio vaccine campaigns conducted between 1957-1960 in Africa on over 1 million inhabitants to blame? Believe it or not, the debate is far from over.

[This paper was originally titled "A Strange Case of Certainty" and republished with the author's permission.]

Abstract

read more

PMID:  Nutrients. 2023 Apr 1 ;15(7). Epub 2023 Apr 1. PMID: 37049574 Abstract Title:  Renal-Protective Roles of Lipoic Acid in Kidney Disease. Abstract:  The kidney is a crucial organ that eliminates metabolic waste and reabsorbs nutritious elements. It also participates in the regulation of blood pressure, maintenance of electrolyte balance and blood pH homeostasis, as well as erythropoiesis and vitamin D maturation. Due to such a heavy workload, the kidney is an energy-demanding organ and is constantly exposed to endogenous and exogenous insults, leading to the development of either acute kidney injury (AKI) or chronic kidney disease (CKD). Nevertheless, there are no therapeutic managements to treat AKI or CKD effectively. Therefore, novel therapeutic approaches for fighting kidney injury are urgently needed. This review article discusses the role of-lipoic acid (ALA) in preventing and treating kidney diseases. We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled. The animal models covered include diabetic nephropathy, sepsis-induced kidney injury, renal ischemic injury, unilateral ureteral obstruction, and kidney injuries induced by folic acid and metals such as cisplatin, cadmium, and iron. We highlight the common mechanisms of ALA's renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death. It is by these mechanisms that ALA achieves its biological function of alleviating kidney injury and improving kidney function. Nevertheless, we also point out that more comprehensive, preclinical, and clinical studies will be needed to make ALA a better therapeutic agent for targeting kidney disorders.

read more

PMID:  Health Sci Rep. 2023 Apr ;6(4):e1186. Epub 2023 Apr 3. PMID: 37021013 Abstract Title:  The efficacy of alpha-lipoic acid in the management of burning mouth syndrome: An updated systematic review of randomized controlled clinical trials. Abstract:  BACKGROUND AND AIMS: Burning mouth syndrome (BMS) causes burning or uncomfortable feelings in the oral cavity without any obvious injuries. This condition's etiopathogenesis is still unknown, consequently, BMS management is very challenging. Alpha-lipoic acid (ALA) is a naturally occurring potent bioactive compound that has been found to be useful in the management of BMS in many studies. Therefore, we conducted a comprehensive systematic review to investigate the usefulness of ALA in the management of BMS based on randomized controlled trials (RCTs).METHODS: Different electronic databases, including PubMed, Scopus, Embase, Web of Science, and Google Scholar, were extensively searched to find relevant studies.RESULTS: This study included nine RCTs that matched the inclusion criteria. In most studies, ALA was given at a dose of 600-800mg/day, with up to two months of follow-up. The majority of studies (six out of nine studies) indicated that ALA was more effective in BMS patients than in the placebo-controlled group.CONCLUSIONS: This comprehensive systematic review provides evidence of the positive outcomes of the treatment of BMS with ALA. However, more research might be needed before ALA can be considered the first-line therapy for BMS.

read more

PMID:  Neurochem Res. 2023 Aug ;48(8):2476-2489. Epub 2023 Apr 5. PMID: 37017891 Abstract Title:  Alpha-Lipoic Acid Ameliorates Doxorubicin-Induced Cognitive Impairments by Modulating Neuroinflammation and Oxidative Stress via NRF-2/HO-1 Signaling Pathway in the Rat Hippocampus. Abstract:  Chemotherapy-induced cognitive impairment (CICI) is a common complication associated with the use of chemotherapeutics. Doxorubicin (DOX) is a reactive oxygen species (ROS) producing anticancer agent capable of causing potential neurotoxic effects via cytokine-induced oxidative and nitrosative damage to brain tissues. On the other hand, alpha-lipoic acid (ALA), a nutritional supplement, is reputable for its excellent antioxidant, anti-inflammatory, and anti-apoptotic activities. Consequently, the objective of the current investigation was to examine any potential neuroprotective and memory-improving benefits of ALA against DOX-induced behavioral and neurological anomalies. DOX (2 mg/kg/week, i.p.) was administrated for 4 weeks to Sprague-Dawley rats. ALA (50, 100, and 200 mg/kg) was administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NORT) tests were used to assess memory function. Biochemical assays with UV-visible spectrophotometry were used to analyze oxidative stress markers [malondialdehyde (MDA), protein carbonylation (PCO)], endogenous antioxidants [reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] and acetylcholinesterase (AChE) activity in hippocampal tissue. Inflammatory markers [tumor necrosis factor-(TNF-), interleukin-6 (IL-6), and nuclear factor kappa B (NF-B)], nuclear factor erythroid 2-related factor-2 (NRF-2) and hemeoxygenase-1 (HO-1) levels were estimated using enzyme-linked immunosorbent assay (ELISA). In addition, reactive oxygen species (ROS) levels were measured in hippocampus tissue using 2-7-dichlorofluorescein-diacetate (DCFH-DA) assay with fluorimetry. ALA treatment significantly protected against DOX-induced memory impairment. Furthermore, ALA restored hippocampal antioxidants, halted DOX-induced oxidative and inflammatory insults via upregulation of NRF-2/HO-1 levels, and alleviated the increase in NF-B expression. These results indicate that ALA offers neuroprotection against DOX-induced cognitive impairment, which could be attributed to its antioxidant potential via the NRF-2/HO-1 signaling pathway.

read more

PMID:  ARYA Atheroscler. 2022 Jul ;18(4):1-8. PMID: 36817351 Abstract Title:  Effects of alpha lipoic acid supplementation on serum lipid profile in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial. Abstract:  BACKGROUND: Alpha lipoic acid (ALA) is considered a strong antioxidant with anti-inflammatory properties. Moreover, a number of previous studies have shown its lipid-lowering properties. Therefore, we designed this study to investigate the effects of ALA on lipid profile in patients with metabolic syndrome (MetS), which can lead to an increased risk of cardiovascular disease (CVD) and premature mortality.METHODS: A total 46 patients with MetS were randomly divided into two groups. They received either 600 mg ALA (n = 23) or 600 mg placebo (n = 23) for 12 weeks. The body weight, height, body mass index (BMI), waist circumference (WC), fasting blood sugar (FBS), hemoglobin A1C (HbA1c), and blood pressure (BP) were assessed at baseline of the study. Physical activity level and dietary intake were assessed at baseline and end of the study. Serum lipid profile including triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were measured before and after 12 weeks of intervention.RESULTS: Baseline characteristics were similar in the ALA and placebo groups (P>0.05). However, there were statistically significant differences in plasma levels of TG (-36.8242.48 versus 6.1525.04 mg/dl, P = 0.001) and TC (-8.9120.65 versus 10.8422.97 mg/dl, P = 0.01) after 12 weeks between the ALA group and the placebo group. Yet, there were no statistically significant differences in plasma levels of HDL-C and LDL-C after 12 weeks between the ALA group and the placebo group.CONCLUSION: The results suggest that daily supplementation of 600 mg ALA for 12 weeks may improve the lipid profile in patients with MetS.

read more

PMID:  J Clin Psychopharmacol. 2023 Jan-Feb 01;43(1):39-45. PMID: 36584248 Abstract Title:  -Lipoic Acid as Adjunctive Treatment for Schizophrenia: A Randomized Double-Blind Study. Abstract:  BACKGROUND/PURPOSE: There is evidence for low endogenous antioxidant levels and oxidative imbalance in patients with schizophrenia. A previous open-label study with-lipoic acid (ALA), a potent antioxidant, improved patients' negative and cognitive symptoms and markers of lipid peroxidation. Here we report the results of a randomized double-blind, placebo-controlled study to verify the response of patients with schizophrenia to adjunctive treatment with ALA (100 mg/d) in a 4-month follow-up.METHODS: We conducted a 16-week, double-blind, placebo-controlled study of ALA at 100 mg/d dosages. We compared negative and positive symptoms, cognitive function, extrapyramidal symptoms, body mass index, and oxidative/inflammatory parameters between placebo and control groups.RESULTS: We found no significant improvement in body mass index, cognition, psychopathology, antipsychotic adverse effects, or oxidative stress and inflammation in the experimental group compared with placebo. The whole group of patients improved in several measures, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in red blood cells, white blood cells, and platelets in the group treated with ALA.CONCLUSIONS: The decrease in red blood cells, white blood cells, and platelet counts requires further investigation and attention when prescribing ALA for patients with schizophrenia.

read more

PMID:  Antioxidants (Basel). 2022 Dec 8 ;11(12). Epub 2022 Dec 8. PMID: 36552628 Abstract Title:  Alpha-Lipoic Acid as an Antioxidant Strategy for Managing Neuropathic Pain. Abstract:  Neuropathic pain (NP) is the most prevalent and debilitating form of chronic pain, caused by injuries or diseases of the somatosensory system. Since current first-line treatments only provide poor symptomatic relief, the search for new therapeutic strategies for managing NP is an active field of investigation. Multiple mechanisms contribute to the genesis and maintenance of NP, including damage caused by oxidative stress. The naturally occurring antioxidant alpha-lipoic acid (ALA) is a promising therapeutic agent for the management of NP. Several pre-clinical in vitro and in vivo studies as well as clinical trials demonstrate the analgesic potential of ALA in the management of NP. The beneficial biological activities of ALA are reflected in the various patents for the development of ALA-based innovative products. This review demonstrates the therapeutic potential of ALA in the management of NP by discussing its analgesic effects by multiple antioxidant mechanisms as well as the use of patented ALA-based products and how technological approaches have been applied to enhance ALA's pharmacological properties.

read more

PMID:  J Agric Food Chem. 2022 Dec 21 ;70(50):15962-15971. Epub 2022 Dec 2. PMID: 36459405 Abstract Title:  -Lipoic Acid Alleviated Fluoride-Induced Hepatocyte Injury via Inhibiting Ferroptosis. Abstract:  Fluoride is widely used in agricultural production and food packaging. Excessive fluoride in water and food is a serious threat to liver health.-Lipoic acid, a natural free radical scavenger, has hepatoprotective properties. However, the protective effect of-lipoic acid on fluorohepatotoxicity is uncertain. The aim of this study was to investigate the mechanism of ferroptosis in-lipoic acid preventing fluoride-induced hepatotoxicity. Five-week-old ICR mice were treated with sodium fluoride (100 mg/L) and/or-lipoic acid (200 mg/kg) for 9 weeks. The results showed that-lipoic acid attenuated fluoride-induced damage to liver morphology and ultrastructure. Moreover,-lipoic acid alleviated fluoride-induced iron accumulation, increased oxidative stress, and elevated lipid peroxidation in the liver. In addition, the mechanism study found that-lipoic acid prevented fluoride-induced ferroptosis through the System Xc/GPX4 axis, lipid peroxidation axis, and iron metabolism axis, but it was interestingly not regulated by mitochondrial free radical axis in the hepatocytes. Altogether, this study indicated that-lipoic acid prevents fluoride-induced liver injury by inhibiting ferroptosis, which has potential implications for the prevention and treatment of fluoride-induced liver injury.

read more

There is a widely held belief amongst patients that doctors should be solely working for the patient's personal good health. This is a myth.

Originally published on www.orthomolecular.org by Sarah Myhill, MBBS

read more

PMID:  Int J Environ Res Public Health. 2023 Mar 7 ;20(6). Epub 2023 Mar 7. PMID: 36981595 Abstract Title:  Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes. Abstract:  BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels.METHODS: Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated.RESULTS: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (

read more

PMID:  Int J Inflam. 2023 ;2023:5480199. Epub 2023 Mar 11. PMID: 36941865 Abstract Title:  N-Acetylcysteine Decreases Myocardial Content of Inflammatory Mediators Preventing the Development of Inflammation State and Oxidative Stress in Rats Subjected to a High-Fat Diet. Abstract:  Arachidonic acid (AA) is a key precursor for proinflammatory and anti-inflammatory derivatives that regulate the inflammatory response. The modulation of AA metabolism is a target for searching a therapeutic agent with potent anti-inflammatory action in cardiovascular disorders. Therefore, our study aims to determine the potential preventive impact of N-acetylcysteine (NAC) supplementation on myocardial inflammation and the occurrence of oxidative stress in obesity induced by high-fat feeding. The experiment was conducted for eight weeks on male Wistar rats fed a standard chow or a high-fat diet (HFD) with intragastric NAC supplementation. The Gas-Liquid Chromatography (GLC) method was used to quantify the plasma and myocardial AA levels in the selected lipid fraction. The expression of proteins included in the inflammation pathway was measured by the Western blot technique. The concentrations of arachidonic acid derivatives, cytokines and chemokines, and oxidative stress parameters were determined by the ELISA, colorimetric, and multiplex immunoassay kits. We established that in the left ventricle tissue NAC reduced AA concentration, especially in the phospholipid fraction. NAC administration ameliorated the COX-2 and 5-LOX expression, leading to a decrease in the PGE2 and LTC4 contents, respectively, and augmented the 12/15-LOX expression, increasing the LXA4 content. In obese rats, NAC ameliorated NF-B expression, inhibiting the secretion of proinflammatory cytokines. NAC also affected the antioxidant levels in HFD rats through an increase in GSH and CAT contents with a simultaneous decrease in the levels of 4-HNE and MDA. We concluded that NAC treatment weakens the NF-B signaling pathway, limiting the development of myocardial low-grade inflammation, and increasing the antioxidant content that may protect against the development of oxidative stress in rats with obesity induced by an HFD.

read more

PMID:  ACS Omega. 2023 Jun 20 ;8(24):21696-21708. Epub 2023 Jun 5. PMID: 37360438 Abstract Title:  Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect ofLeaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies. Abstract:  The present study analyzes the efficacy of the ethanolic extract ofleaves (ECP) against HgCl-induced nephrotoxicity. The effects on the biochemical and percentage of body and organ weight against HgCl-induced nephrotoxicity in female Wistar rats were studied. Wistar rats were divided into five groups with six animals in each group: control, HgCl(2.5 mg/kg b.w.),-acetylcysteine (NAC 180 mg/kg) + HgCl, ECP (300 mg/kg b.w.) + HgCl, and ECP (600 mg/kg) + HgClgroups. After 28 days of study, animals were sacrificed on the 29th day to harvest the blood and kidneys for further analysis. The effect ECP was analyzed by immunohistochemistry (NGAL) and real-time PCR (KIM-1 and NGAL mRNA) in HgCl-induced nephrotoxicity. The results revealed that the HgClgroup showed prominent damage in the proximal tubules and glomerulus of nephrons and enormous expression of NGAL in immunohistochemistry and KIM-1 and NGAL in real-time PCR compared to the control group. The simultaneous pretreatment with NAC (180 mg/kg) and ECP (600 and 300 mg/kg) reduced renal damage and expression of NGAL in immunohistochemistry and KIM-1 and NGAL gene in real-time PCR. This study attests to the nephroprotective effect of ECP against HgCl-induced toxicity.

read more

The ApoE4 Exaggeration

Originally published on www.orthomolecular.org by Patrick Holford

The ApoE4 Exaggeration

read more

The remarkable clinical versatility of Nigella sativa

Originally published on www.orthomolecular.org by Max Langen

The remarkable clinical versatility of Nigella sativa

read more

The World Health Organization and their "One Health" approach are coming for the world's food systems, aiming to meld them with health and medical fields

Originally published on www.mercola.com

Video Link

STORY AT-A-GLANCE

read more

Occasionally a doctor or a nutritionist will write an article and express the opinion that people do not need to use special diets or nutritional supplements to encourage the removal of toxins from the body. Their view is that the body has a perfectly designed detoxification system using the liver and our skin to remove any toxins. In theory that may be correct, but in practice it is "dead" wrong, with pun intended. Here are some questions for the misinformed:

read more

Over 10,000 categories of nearly 1.6 million adverse events - many of them serious and debilitating - brought to you by Pfizer!

Originally published on www.conservativereview.com by Daniel Horowitz

Over 10,000 categories of nearly 1.6 million adverse events - many of them serious and debilitating - brought to you by Pfizer!

read more