title: Protective effects of resveratrol on hepatotoxicity induced by isoniazid and rifampicin via SIRT1 modulation.
abstract: 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.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, ‡Programa de Pós-Graduação em Biologia Celular e Molecular, §Programa de Pós-Graduação em Medicina e Ciências da Saúde, ∥Instituto de Toxicologia e Farmacologia, ⊥Faculdade de Odontologia, and #Faculdade de Química, Pontifical Catholic University of Rio Grande do Sul (PUCRS) , Porto Alegre, RS Brazil.
authors.forename: Natália F
authors.initials: NF
authors.lastname: Nicoletti
authors.forename: Valnês
authors.initials: V
authors.lastname: Rodrigues-Junior
authors.forename: André A
authors.initials: AA
authors.lastname: Santos
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Leite
authors.forename: Ana C O
authors.initials: AC
authors.lastname: Dias
authors.forename: Eraldo L
authors.initials: EL
authors.lastname: Batista
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Basso
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: Diógenes S
authors.initials: DS
authors.lastname: Santos
authors.forename: André A
authors.initials: AA
authors.lastname: Souto
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D007538:Isoniazid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077185:Resveratrol; D012293:Rifampin / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013267:Stilbenes; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005978:Glutathione; D000077185:Resveratrol; D007538:Isoniazid; D012293:Rifampin