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

• Published in: Journal of natural products (Washington, D.C.) Vol. 77; no. 10; pp. 2190 - 2195
• Main Authors: Nicoletti, Natália F, Rodrigues-Junior, Valnês, Santos, André A, Leite, Carlos E, Dias, Ana C. O, Batista, Eraldo L, Basso, Luiz A, Campos, Maria M, Santos, Diógenes S, Souto, André A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 24.10.2014
• Subjects: Alanine Transaminase - blood; Alanine Transaminase - drug effects; Animals; Antitubercular Agents - pharmacology; Aspartate Aminotransferases - blood; Aspartate Aminotransferases - drug effects; Chemical and Drug Induced Liver Injury; Glutathione - metabolism; Interleukin-10 - analysis; Interleukin-10 - metabolism; Isoniazid - pharmacology; Liver - drug effects; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Oxidation-Reduction; Oxidative Stress - drug effects; Peroxidase - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR gamma - drug effects; Rifampin - pharmacology; Sirtuin 1 - drug effects; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stilbenes - pharmacology; Transcription Factors - drug effects; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np5003143

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–rifampicin in mice. Compound 1 was administered 30 min prior to isoniazid–rifampicin. Serum biochemical tests, liver histopathological examination, oxidative stress, myeloperoxidase activity, cytokine production (TNF-α, IL-12p70, and IL-10), and mRNA expression of SIRT1–7 and PPAR-γ/PGC1-α 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-γ/PGC1-α 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.