PMID: 

Annu Rev Physiol. 2019 Nov 18. Epub 2019 Nov 18. PMID: 31738670

Abstract Title: 

Gestational Exposure to Common Endocrine Disrupting Chemicals and Their Impact on Neurodevelopment and Behavior.

Abstract: 

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes: bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data. Expected final online publication date for the, Volume 82 is February 10, 2020. Please see https://ift.tt/2CYBVUj for revised estimates.

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PMID: 

Interdiscip Toxicol. 2018 Oct ;11(3):209-216. Epub 2019 Oct 18. PMID: 31736635

Abstract Title: 

analysis of Bisphenol A induced dose-dependent adverse effects in cauda epididymis of mice.

Abstract: 

Bisphenol A is widely used as a material for the production of epoxy resins and polycarbonate plastics. It contaminates various food stuffs by getting leached out from their container lining. Limited information is available on its effects on the male reproductive system. The aim of the present study was to evaluate the extent to which bisphenol A can affect the reproductive system by measuring biochemical and histological changes in the epididymis. Inbred Swiss strain male albino mice were orally administered 80, 120 and 240 mg/kg body weight/day of BPA for 45 days. After completion of treatment, the animals were sacrificed; cauda epididymis was isolated, weighed, used for biochemical and histopathological studies. The results revealed that BPA administered for 45 days caused significant (0.05) and dose-dependent reduction in epididymis weight. There was significant (0.05) increase in lipid peroxidation and the acid phosphatase activity. Dose dependent reduction in protein, sialic acid contents, as well as the activity of enzymatic antioxidants and mitochondrial enzymes was recorded compared to vehicle treated group. The effect was dose-dependent. Histopathological alteration was observed. This study concludes that BPA causes toxicity in epididymis of mice by generating free radicals, which may be a possible reason for reduction in sperm parameters.

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PMID: 

Rev Environ Health. 2019 Nov 19. Epub 2019 Nov 19. PMID: 31743105

Abstract Title: 

A review on sources and health impacts of bisphenol A.

Abstract: 

Bisphenol-A (BPA) is a synthetic chemical used in the manufacturing of polycarbonates and epoxy resins. This paper is a review of studies reporting the occurrences and concentrations of BPA in the environment and associated impact on human health. Studies have found that at high temperature conditions such as open burning of dumped waste in developing nations can relocate BPA from plastic waste into the environment. BPA is a proven endocrine disruptor capable of mimicking or blocking the receptors and altering hormone concentrations and its metabolism. Even though it is consumed in a low dose, it can stimulate cellular responses and affect body functions. Biomonitoring studies show that human and animal exposure to BPA is rapid and continuous. In-depth studies are needed to understand the fate of these compounds particularly in the developing nations and the associated adverse health impacts of BPA due to prolonged exposure.

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PMID: 

Chemosphere. 2019 Oct 8 ;241:125077. Epub 2019 Oct 8. PMID: 31614311

Abstract Title: 

Triclosan stimulates human vascular endothelial cell injury via repression of the PI3K/Akt/mTOR axis.

Abstract: 

Triclosan (TCS) has potentially toxic effects on humans and animals. However, the possible roles and mechanisms of TCS in endothelial cells (ECs) are still unknown. Abnormal damage to ECs and vascular function is a critical process in various cardiovascular diseases, including coronary artery disease (CAD), atherosclerosis, stroke, and hypertension. Hence, we explored the potential toxicological roles of TCS in EC functions. Cell Counting Kit-8, apoptosis, transwell, wound healing, and tube-formation experiments were performed to evaluate the effects of TCS on human umbilical vein endothelial cell (HUVEC) function. Additionally, the levels of PI3K, Akt, and mTOR phosphorylation were measured by Western blot. The results indicated that TCS treatment suppressed HUVECs viability, migration and angiogenesis. TCS treatment increased the expression of inflammatory markers and ROS in cultured HUVECs. Moreover, TCS treatment inhibited PI3K/Akt/mTOR expression. All of these results reveal that TCS induces notable vascular injury and affects the viability, migration and angiogenic capacity of HUVECs, at least in part via the PI3K/Akt/mTOR signaling pathway.

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PMID: 

J Hazard Mater. 2019 Sep 24 ;384:121310. Epub 2019 Sep 24. PMID: 31586915

Abstract Title: 

Lipid metabolism disorders contribute to hepatotoxicity of triclosan in mice.

Abstract: 

Previous in vivo exposure studies focused mainly on nuclear receptors involved in hepatotoxicity of triclosan (TCS). As liver plays a vital role in metabolic processes, dysregulations in lipid metabolism have been identified as potential drivers of pathogenesis. Investigation of changes in lipid metabolism might widen our understanding of toxicological effects as well as the underlying mechanism occurring in the liver. In this study, we comprehensively assessed the effect of TCS exposure on hepatic lipid metabolism in mice. Our results showed that TCS induced significant changes in hepatic free fatty acid pool by upregulation of fatty acid uptake and de novo fatty acid synthesis. Besides, hepatic levels of lipids, including acyl carnitine (AcCa), ceramide (Cer), triacylglycerols (TG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) were also increased, together with upreguation of genes associated to TG synthesis, fatty acid oxidation and inflammation in TCS exposure group. These changes in lipid homeostasis could contribute to membrane instability, lipid accumulation, oxidative stress and inflammation. Our results suggested that TCS exposure could induce hepatic lipid metabolism disorders in mice, which would further contribute to the liver damage effects of TCS.

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PMID: 

Nutr Metab Cardiovasc Dis. 2019 Nov ;29(11):1151-1167. Epub 2019 Jul 24. PMID: 31561944

Abstract Title: 

Efficacy of l-carnitine supplementation for management of blood lipids: A systematic review and dose-response meta-analysis of randomized controlled trials.

Abstract: 

BACKGROUND AND AIM: l-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles.METHODS AND RESULTS: We performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model. In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: -8.53 mg/dl, 95% CI: -13.46, -3.6, I: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: -5.48 mg/dl, 95% CI: -8.49, -2.47, I: 94.5) and triglyceride (TG) (56 arms-MD: -9.44 mg/dl, 95% CI: -16.02, -2.87, I: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides.CONCLUSION: l-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.

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PMID: 

Dig Liver Dis. 2019 Oct 10. Epub 2019 Oct 10. PMID: 31607566

Abstract Title: 

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disorder. NAFLD, associated lipotoxicity, fibrosis, oxidative stress, and altered mitochondrial metabolism, is responsible for systemic inflammation, which contributes to organ dysfunction in extrahepatic tissues, including the heart. We investigated the ability of L-carnitine (LC) to oppose the pathogenic mechanisms underlying NAFLD progression and associated heart dysfunction, in a mouse model of methionine-choline-deficient diet (MCDD). Mice were divided into three groups: namely, the control group (CONTR) fed with a regular diet and two groups fed with MCDD for 6 weeks. In the last 3 weeks, one of the MCDD groups received LC (200 mg/kg each day) through drinking water (MCDD + LC). The hepatic lipid accumulation and oxidative stress decreased after LC supplementation, which also reduced hepatic fibrosis via modulation of α-smooth muscle actin (αSMA), peroxisome-activated receptor gamma (PPARγ), and nuclear factor kappa B (NfƙB) expression. LC ameliorated systemic inflammation, mitigated cardiac reactive oxygen species (ROS) production, and prevented fibrosis progression by acting on signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1-2 (ERK1-2), and αSMA. This study confirms the existence of a relationship between fatty liver disease and cardiac abnormalities and highlights the role of LC in controlling liver oxidative stress, steatosis, fibrosis, and NAFLD-associated cardiac dysfunction.

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PMID: 

EXCLI J. 2019 ;18:631-643. Epub 2019 Aug 19. PMID: 31611746

Abstract Title: 

The effects of L-carnitine supplementation on glycemic control: a systematic review and meta-analysis of randomized controlled trials.

Abstract: 

The findings of trials investigating the effect of L-carnitine administration on glycemic control are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of L-carnitine intake on glycemic control. Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, Web of Science, PubMed and Google scholar from 1990 until February 2019, in order to find relevant RCTs. 37 studies with 44 effect sizes met the inclusion criteria and were eligible for the meta-analysis. L-carnitine supplementation resulted in a significant reduction in fasting plasma glucose (FPG) (WMD: -4.57; 95 % CI: -6.88, -2.25), insulin (WMD: -1.21; 95 % CI: -1.85, -0.57), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.67; 95 % CI: -0.90, -0.44) and HbA1C concentrations (WMD: -0.30; 95 % CI: -0.47, -0.13). L-Carnitine supplementation significantly reduced FPG, insulin, HOMA-IR, and HbA1c levels.

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PMID: 

Can J Physiol Pharmacol. 2019 Oct 30. Epub 2019 Oct 30. PMID: 31665614

Abstract Title: 

Protective Effects of Olmesartan and L-carnitine on Doxorubicin-Induced Cardiotoxicity in Rats.

Abstract: 

Doxorubicin (DOX), anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in hematological, as well as in solid malignancies. The present study aimed to investigate the possible protective effect of olmesartan (Olm), L-carnitine (L-CA) and their combination in cardiotoxicity induced by doxorubicin (DOX) in rats. Male albino rats were randomly divided into seven experimental groups (n=8): Group I: normal control, group II: L-CA, Group III: Olm, Group IV: DOX. The other three groups were treated with Olm (10 mg/kg), L-CA (300 mg/kg) and their combination for 2 weeks, after induction of cardiotoxicity by a single dose of DOX (20 mg/kg). In results, DOX showed a significant elevation in serum troponin I, CK-MB, and LDH, together with increased inflammation manifested by the rise of TNF-α, ICAM-1, IL-1, MPO, NF-k β and TGF-β in cardiac tissues. While, DOX-induced oxidative stress by increasing in MDA and decreasing in SOD and GSH in heart tissues. In addition, caspase-3 activity was boosted as indication of increased apoptosis. On the other hand, administration of L-CA and Olm attenuated the DOX-evoked disturbances in the above mentioned parameters. In addition, DOX exhibited echocardiographic changes and severe histopathological changes, which were significantly reversed by L-CA and Olm treatment. In conclusion, the present study data confirms the protective role of L-CAand Olm in DOX-induced cardiotoxicity.

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PMID: 

EBioMedicine. 2019 Nov ;49:318-330. Epub 2019 Oct 31. PMID: 31676389

Abstract Title: 

Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.

Abstract: 

BACKGROUND: Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers.METHODS: Eleven IGT- volunteers followed a 36-day placebo- and L-carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group.RESULTS: Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected.CONCLUSION: Carnitine supplementation improves acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.

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