Early-life Exposure to Bisphenol a Induces Liver Injury in Rats Involvement of Mitochondria-mediated Apoptosis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 4

PMID 24587367

Citations 35

Authors

Wei Xia

Ying Jiang

Yuanyuan Li

Yanjian Wan

Juan Liu

Yue Ma

Zhenxing Mao

Huailong Chang

Gengqi Li

Bing Xu

Xi Chen

Shunqing Xu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Bisphenol A (BPA) and Cardiovascular or Cardiometabolic Diseases.

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References

Marmugi A, Ducheix S, Lasserre F, Polizzi A, Paris A, Priymenko N . Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver. Hepatology. 2011; 55(2):395-407. DOI: 10.1002/hep.24685. View

Cotney J, McKay S, Shadel G . Elucidation of separate, but collaborative functions of the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 in mitochondrial biogenesis reveals new insight into maternally inherited deafness. Hum Mol Genet. 2009; 18(14):2670-82. PMC: 2701340. DOI: 10.1093/hmg/ddp208. View

Vandenberg L, Maffini M, Sonnenschein C, Rubin B, Soto A . Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev. 2008; 30(1):75-95. PMC: 2647705. DOI: 10.1210/er.2008-0021. View

Yamada H, Furuta I, Kato E, Kataoka S, Usuki Y, Kobashi G . Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester. Reprod Toxicol. 2002; 16(6):735-9. DOI: 10.1016/s0890-6238(02)00051-5. View

Shimizu S, Narita M, Tsujimoto Y . Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 1999; 399(6735):483-7. DOI: 10.1038/20959. View

Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y . Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice. Reprod Toxicol. 2002; 16(2):107-16. DOI: 10.1016/s0890-6238(02)00005-9. View

Vaux D . Apoptogenic factors released from mitochondria. Biochim Biophys Acta. 2010; 1813(4):546-50. DOI: 10.1016/j.bbamcr.2010.08.002. View

Asahi J, Kamo H, Baba R, Doi Y, Yamashita A, Murakami D . Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes. Life Sci. 2010; 87(13-14):431-8. DOI: 10.1016/j.lfs.2010.08.007. View

Susin S, Zamzami N, Kroemer G . Mitochondria as regulators of apoptosis: doubt no more. Biochim Biophys Acta. 1998; 1366(1-2):151-65. DOI: 10.1016/s0005-2728(98)00110-8. View

10.

Dini L, Pagliara P, Carla E . Phagocytosis of apoptotic cells by liver: a morphological study. Microsc Res Tech. 2002; 57(6):530-40. DOI: 10.1002/jemt.10107. View

11.

Guicciardi M, Gores G . Apoptosis: a mechanism of acute and chronic liver injury. Gut. 2005; 54(7):1024-33. PMC: 1774601. DOI: 10.1136/gut.2004.053850. View

12.

Kluck R, Bossy-Wetzel E, Green D, Newmeyer D . The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997; 275(5303):1132-6. DOI: 10.1126/science.275.5303.1132. View

13.

Liu J, Yu P, Qian W, Li Y, Zhao J, Huan F . Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure. PLoS One. 2013; 8(5):e64143. PMC: 3651242. DOI: 10.1371/journal.pone.0064143. View

14.

Lang I, Galloway T, Scarlett A, Henley W, Depledge M, Wallace R . Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008; 300(11):1303-10. DOI: 10.1001/jama.300.11.1303. View

15.

Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y . Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod. 2002; 17(11):2839-41. DOI: 10.1093/humrep/17.11.2839. View

16.

Kroemer G, Galluzzi L, Brenner C . Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007; 87(1):99-163. DOI: 10.1152/physrev.00013.2006. View

17.

Volkel W, Colnot T, Csanady G, Filser J, Dekant W . Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. Chem Res Toxicol. 2002; 15(10):1281-7. DOI: 10.1021/tx025548t. View

18.

Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, Quesada I . Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect. 2010; 118(9):1243-50. PMC: 2944084. DOI: 10.1289/ehp.1001993. View

19.

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

20.

Kundakovic M, Gudsnuk K, Franks B, Madrid J, Miller R, Perera F . Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc Natl Acad Sci U S A. 2013; 110(24):9956-61. PMC: 3683772. DOI: 10.1073/pnas.1214056110. View