Protective Effects of Resveratrol on Hepatotoxicity Induced by Isoniazid and Rifampicin via SIRT1 Modulation

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• 作者：Nat谩lia F. Nicoletti ; Valn锚s Rodrigues-Junior ; Andr茅 A. Santos ; Jr. ; Carlos E. Leite ; Ana C. O. Dias ; Eraldo L. Batista ; Jr. ; Luiz A. Basso ; Maria M. Campos ; Di贸genes S. Santos ; Andr茅 A. Souto
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：October 24, 2014
• 年：2014
• 卷：77
• 期：10
• 页码：2190-2195
• 全文大小：373K
• ISSN：1520-6025

文摘

Acute liver injury was induced in male BALB/c mice by coadministering isoniazid and rifampicin. In this work, the effects of resveratrol (1) were investigated in the hepatotoxicity caused by isoniazid鈥搑ifampicin in mice. Compound 1 was administered 30 min prior to isoniazid鈥搑ifampicin. Serum biochemical tests, liver histopathological examination, oxidative stress, myeloperoxidase activity, cytokine production (TNF-伪, IL-12p70, and IL-10), and mRNA expression of SIRT1鈥? and PPAR-纬/PGC1-伪 were evaluated. The administration of 1 significantly decreased aspartate transaminase and alanine aminotransferase levels, myeloperoxidase activity, and cytokine levels. Furthermore, 1 reverted the decrease of catalase and glutathione activities and ameliorated the histopathological alterations associated with antituberculosis drugs. Modulation of SIRT1 and PPAR-纬/PGC1-伪 expression is likely involved in the protective effects of 1. The results presented herein show that 1 was able to largely prevent the hepatotoxicity induced by isoniazid and rifampicin in mice, mainly by modulating SIRT1 mRNA expression.