PCB28 and PCB52 induce hepatotoxicity by impairing the autophagic flux and stimulating cell apoptosis in vitro.
Toxicol Lett
; 289: 28-41, 2018 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-29518472
ABSTRACT
Hepatotoxicity is one of the adverse health effects induced by polychlorinated biphenyls (PCBs). Recently, autophagy was revealed to play an important role in PCBs-induced toxicology, however, its precise role in PCBs-induced hepatotoxicity is as yet unknown. In this study, treatment of PCB28/PCB52 for 48â¯h dose-dependently induced hepatotoxicity at doses of 10, 20, 40 and 80⯵M in homo and rattus hepatocytes. Expressions of proteins of BECN1, LC3-II and ULK1 significantly increased in PCB28/PCB52-treated cells at a dose of 40⯵M, implying initiation of autophagy. Over-expression of p62 suggested deficient clearance of autophagosome. Consistently, accumulation of autophagosome was observed by transmission-electron microscopy and confocal fluorescence microscopy using adenovirus expressing mRFP-GFP-LC3, which may initiate apoptosis. Furthermore, increased reactive oxygen species levels might also induce autophagy and apoptosis. Consistently, cell apoptosis was evoked by the treatment of PCB28/PCB52 compared to the respective controls, which coincided with obvious hepatotoxicity. Subsequently, an inhibitor (3-methlyadenine) and an initiator (rapamycin) of autophagy were used. Compared to PCB28/PCB52 alone-treated cells, initiation of autophagy, blocked autophagic flux, cell apoptosis and hepatotoxicity were alleviated by 3-methlyadenine and aggravated by rapamycin, respectively. Taken together, PCB28 and PCB52 induced hepatotoxicity by impairing autophagic flux and stimulating cell apoptosis in vitro.
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MEDLINE
Assunto principal:
Autofagia
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Regulação da Expressão Gênica
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Bifenilos Policlorados
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Apoptose
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Hepatócitos
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Poluentes Ambientais
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article