DOI: 10.62425/jlasp.1932861 ISSN: 2791-8645

Protective Effects of Folic Acid Against Indomethacin-Induced Liver Injury: Involvement of Nrf2/HO-1, NF-κB, and Apoptotic Signaling Pathways

Ender Erdoğan, Özge Kandemir
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The aim of protective role of folic acid (FA) against indomethacin (IND)-induced hepatotoxicity in rats. In particular, the study focused on the capacity of FA to mitigate oxidative stress-related hepatic injury. The results demonstrated that FA treatment markedly attenuated liver damage when compared with the untreated control group. Antioxidant defense system revealed that IND administration led to significant reduction in catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities, together with decreased glutathione (GSH) levels, whereas these parameters were improved following FA treatment. Moreover, FA administration lowered malondialdehyde (MDA) concentrations, an important indicator of lipid peroxidation. FA also exhibited notable anti-inflammatory effects by suppressing proinflammatory mediators, particularly through downregulation of interleukin-1 beta (IL-1β) expression and inhibition of nuclear factor kappa-B (NF- κB) activation. In addition, FA reduced the IND-induced elevation of the proapoptotic proteins Bcl-2-associated X protein (Bax) and cysteine-aspartic protease-3 (Caspase-3), while enhancing the transcriptional activity of the antiapoptotic gene B-cell lymphoma-2 (Bcl-2). Biochemical analyses further indicated that FA alleviated hepatic tissue injury by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels elevated by IND exposure. With respect to oxidative stress-associated signaling pathways, the IND-treated group exhibited decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels alongside increased Keap1 expression. In contrast, IND+FA group showed a statistically significant increase in Nrf2 and HO-1 levels and a reduction in Keap1 expression relative to the IND group. Overall, these findings suggest that FA exerts a protective effect against IND-induced liver toxicity and may alleviate hepatic damage through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

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