Pyrazinamide induced hepatic injury in rats through inhibiting the PPARα pathway.
J Appl Toxicol
; 36(12): 1579-1590, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27071702
ABSTRACT
Pyrazinamide (PZA) causes serious hepatotoxicity, but little is known about the exact mechanism by which PZA induced liver injury. The peroxisome proliferator-activated receptors alpha (PPARα) is highly expressed in the liver and modulates the intracellular lipidmetabolism. So far, the role of PPARα in the hepatotoxicity of PZA is unknown. In the present study, we described the hepatotoxic effects of PZA and the role of PPARα and its target genes in the downstream pathway including L-Fabp, Lpl, Cpt-1b, Acaa1, Apo-A1 and Me1 in this process. We found PZA induced the liver lipid metabolism disorder and PPARα expressionwas down-regulated which had a significant inverse correlation with liver injury degree. These changeswere ameliorated by fenofibrate, the co-treatment that acts as a PPARα agonist. In contrast, short-termstarvation significantly aggravated the severity of PZA-induced liver injury. In conclusion, this study demonstrated the critical role played by PPARα in PZA-induced hepatotoxicity and provided a better understanding of the molecular mechanisms underlying PZA-induced liver injury. Copyright © 2016 John Wiley & Sons, Ltd.
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Base de dados:
MEDLINE
Assunto principal:
Pirazinamida
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PPAR alfa
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Metabolismo dos Lipídeos
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Doença Hepática Induzida por Substâncias e Drogas
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Fígado
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Antituberculosos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article