Abstract

YETER, Bahtınur et al. Protective effects of thiamine pyrophosphate and cinnamon against oxidative liver damage induced by an isoniazid and rifampicin combination in rats. Invest. clín [online]. 2024, vol.65, n.3, pp.321-334.  Epub Sep 15, 2024. ISSN 0535-5133.  https://doi.org/10.54817/ic.v65n3a05.

Isoniazid and rifampicin (IRC) have been shown to cause hepatotoxicity in both clinical and preclinical studies. Oxidative stress and inflammation have been held responsible for the pathogenesis of IRC-induced hepatotoxicity. Antioxidative and anti-inflammatory effects of thiamine pyrophosphate (TPP) and cinnamon extract (CE) have been shown in previous studies. Therefore, our study investigated the protective effects of TPP and CE on possible liver damage caused by IRC treatment in rats. Twenty-four albino Wistar rats were categorized into four groups: a healthy group (HG), an IRC group (IRG), a TPP+IRC group (TIRG), and a CE+IRC group (CIRG). TPP (25 mg/kg) was administered intraperitoneally to TIRG, while CE (100 mg/kg) was administered orally to CIRG. In IRG, TIRG, and CIRG, isoniazid (50 mg/ kg) and rifampicin (50 mg/kg) were administered orally one hour after these treatments. For seven days, this procedure was repeated once a day. After this period, blood samples were taken from the tail veins, and the rats were sacrificed. The removed liver tissues were analyzed for oxidant, antioxidant, and proinflammatory cytokines and subjected to histopathological evaluation. Serum alanine aminotransferase and aspartate aminotransferase activities were also measured. An increase in malondialdehyde, nuclear factor kappa B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6 levels, a decrease in total glutathione levels, superoxide dismutase and catalase activities, and an increase in alanine aminotransferase and aspartate aminotransferase activities were found with IRC treatment (p<0.001). The histopathological analysis of the IRG suggested hepatotoxicity (p<0.001). TPP and CE administered with IRC inhibited the biochemical changes (p<0.001). In the TIRG, this inhibition was higher than in the CIRG (p<0.05). Histological damage was inhibited by TPP (p<0.001). CE prevented biochemical changes but not histological changes except inflammatory cell infiltration. Therefore, TPP may be better than CE in preventing IRC-induced hepatotoxicity.

Keywords : isoniazid; rifampicin; thiamine pyrophosphate; cinnamon extract; oxidative stress; inflammation.

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