Journal
JOURNAL OF NATURAL PRODUCTS
Volume 77, Issue 10, Pages 2190-2195Publisher
AMER CHEMICAL SOC
DOI: 10.1021/np5003143
Keywords
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Funding
- CNPq [Ed152008 INCTs DI FB]
- FAPERGS-CAPES (DOCFIX) [05/2013]
- FINEP research grant Implantacao, Modernizacao e Qualificacao de Estrutura de Pesquisa da PUCRS (PUCRSIN-FRA) [01.11.0014-00]
- National Institute of Science and Technology on Tuberculosis (DECIT/SCTIE/MS-MCT-CNPq-FNDCT-CAPES)
- Millennium Initiative Program (CNPq)
- National Research Council of Brazil (CNPq)
- BNDES
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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-alpha, IL-12p70, and IL-10), and mRNA expression of SIRT1-7 and PPAR-gamma/PGC1-alpha 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-?/PGC1-a 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.
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