Early-life exposure to bisphenol a induces liver injury in rats involvement of mitochondria-mediated apoptosis

• Published in: PloS one 2014-02, Vol.9 (2), p.e90443
• Main Authors: Xia, Wei, Jiang, Ying, Li, Yuanyuan, Wan, Yanjian, Liu, Juan, Ma, Yue, Mao, Zhenxing, Chang, Huailong, Li, Gengqi, Xu, Bing, Chen, Xi, Xu, Shunqing
• Format: Article
• Language: English
• Subjects: Abnormalities; Alanine Transaminase - blood; Animal experimentation; Animals; Animals, Newborn; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Benzhydryl Compounds - toxicity; Biology; Bisphenol A; Body Weight - drug effects; Caspase; Caspase-3; Caspase-9; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Cytochrome; Cytochrome c; DNA Fragmentation - drug effects; DNA methylation; Education; Environmental health; Environmental protection; Estrogens, Non-Steroidal - toxicity; Exposure; Female; Hepatotoxicity; Laboratories; Lipid Metabolism - drug effects; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Medicine; Metabolism; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial Proteins - metabolism; Neonates; Nuclei; Offspring; Organ Size - drug effects; Pathogenesis; Perinatal exposure; Permeability; Phenols; Phenols (Class of compounds); Phenols - toxicity; Polycarbonate; Polycarbonates; Polymers; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Proteins; Public health; Rats; Rats, Wistar; Rodents; Science; Studies; Time Factors; Triglycerides - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090443

Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.