A systematic comparison of the developmental vascular toxicity of bisphenol A and its alternatives in vivo and in vitro

This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose-dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose-dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

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The Xenoestrogen Bisphenol A Inhibits Postembryonic Vertebrate Development by Antagonizing Gene Regulation by Thyroid Hormone

Endocrinology ◽

10.1210/en.2008-1503 ◽

2009 ◽

Vol 150 (6) ◽

pp. 2964-2973 ◽

Cited By ~ 74

Author(s):

Rachel A. Heimeier ◽

Biswajit Das ◽

Daniel R. Buchholz ◽

Yun-Bo Shi

Keyword(s):

Bisphenol A ◽

Estrogenic Activity ◽

Sex Differentiation ◽

Inhibitory Effect ◽

Vertebrate Development ◽

Developmental Context ◽

Mammalian Embryos ◽

Intestinal Remodeling

Bisphenol A (BPA), a chemical widely used to manufacture plastics, is estrogenic and capable of disrupting sex differentiation. However, recent in vitro studies have shown that BPA can also antagonize T3 activation of the T3 receptor. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. This study proposed to identify critical T3 pathways that may be disrupted by BPA based on molecular analysis in vivo. Because amphibian metamorphosis requires T3 and encompasses the postembryonic period in mammals when T3 action is most critical, we used this unique model for studying the effect of BPA on T3-dependent vertebrate development at both the morphological and molecular levels. After 4 d of exposure, BPA inhibited T3-induced intestinal remodeling in premetamorphic Xenopus laevis tadpoles. Importantly, microarray analysis revealed that BPA antagonized the regulation of most T3-response genes, thereby explaining the inhibitory effect of BPA on metamorphosis. Surprisingly, most of the genes affected by BPA in the presence of T3 were T3-response genes, suggesting that BPA predominantly affected T3-signaling pathways during metamorphosis. Our finding that this endocrine disruptor, well known for its estrogenic activity in vitro, functions to inhibit T3 pathways to affect vertebrate development in vivo and thus not only provides a mechanism for the likely deleterious effects of BPA on human development but also demonstrates the importance of studying endocrine disruption in a developmental context in vivo.

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Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo

Food and Chemical Toxicology ◽

10.1016/j.fct.2017.11.010 ◽

2018 ◽

Vol 111 ◽

pp. 125-132 ◽

Cited By ~ 11

Author(s):

Seoyoung Kim ◽

Gil-im Mun ◽

Eun Choi ◽

Minjeong Kim ◽

Ji Seong Jeong ◽

...

Keyword(s):

Dna Damage ◽

Bisphenol A ◽

Cell Lines ◽

Human Hepatocyte ◽

Juvenile Rats

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Experimental Validation of Plant Peroxisomal Targeting Prediction Algorithms by Systematic Comparison of In Vivo Import Efficiency and In Vitro PTS1 Binding Affinity

Journal of Molecular Biology ◽

10.1016/j.jmb.2014.12.003 ◽

2015 ◽

Vol 427 (5) ◽

pp. 1085-1101 ◽

Cited By ~ 15

Author(s):

Nicola S. Skoulding ◽

Gopal Chowdhary ◽

Mara J. Deus ◽

Alison Baker ◽

Sigrun Reumann ◽

...

Keyword(s):

Binding Affinity ◽

Experimental Validation ◽

Systematic Comparison ◽

Prediction Algorithms ◽

Peroxisomal Targeting

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CTB glycoprotein (75kDa) inhibits IgE releasing, TNF-α and IL-6 expressed by bisphenol A in vivo and in vitro

Food and Chemical Toxicology ◽

10.1016/j.fct.2012.03.043 ◽

2012 ◽

Vol 50 (6) ◽

pp. 2109-2117 ◽

Cited By ~ 11

Author(s):

Jin Lee ◽

Sei-Jung Lee ◽

Kye-Taek Lim

Keyword(s):

Bisphenol A ◽

Tnf Α

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Chronic Exposure to High Doses of Bisphenol A Exhibits Significant Atrial Proarrhythmic Effects in Healthy Adult Rats

Romanian Journal of Cardiology ◽

10.47803/rjc.2021.31.3.587 ◽

2021 ◽

Vol 31 (3) ◽

pp. 587-595

Author(s):

Vasile Bogdan HALATIU ◽

◽

Alkora Ioana BALAN ◽

Dan Alexandru COZAC ◽

Remus BOBARNAC ◽

...

Keyword(s):

Bisphenol A ◽

Chronic Exposure ◽

Atrial Pacing ◽

Autonomic Tone ◽

Adult Rats ◽

Female Wistar Rats ◽

High Doses ◽

Premature Beats

Objectives: We aimed to evaluate the effects of chronic exposure to bisphenol A (BPA) on atrial fibrillation (AF) occurrence in rats. Methods: Twenty-two healthy female Wistar rats were randomized into three groups: Control (no BPA; n=7), BPA (exposed to usual BPA doses; 50 μg/kg/day, 9 weeks; n=7), and hBPA (exposed to high BPA doses; 25 mg/kg/day, 9 weeks; n=8). 24-h ECG monitoring was performed using radiotelemetry ECG devices prior to and after transesophageal atrial pacing. Spontaneous and pacing-induced atrial arrhythmias, autonomic tone, and in vivo an in vitro atrial arrhythmogenicity-related parameters were evaluated. Results: All studied parameters were similar between Control and BPA (all p>0.05). However, compared to Control, hBPA presented more atrial premature beats both at baseline (p=0.04) and after pacing (p=0.03), more AF episodes (p<0.001) and of longer duration (p=0.02) following transesophageal stimulation, and significantly higher vagal tone (all p<0.05). Conclusions: Chronic exposure to high, but not usual BPA doses induced significant atrial proarrhythmic effects in healthy rats, and this may be at least partially due to BPA-induced vagal hyperactivation. Exposure to high BPA doses, such as that occurring in plastics industry workers, could favor AF occurrence even in the absence of underlying cardiovascular disease.

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