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Open AccessResearch Article
Peer Reviewed

Comparative Evaluation of Hepatoprotective Activity of Apigenin and Alpha-Tocopherol Against Methotrexate-Induced Hepatotoxicity in Rats

ByVignesh .V*,Dr.N.Chidambaranathan
Keywords:
MethotrexateHepatotoxicityApigeninAlpha-tocopherolOxidative stressSilymarinWistar rats

Abstract

Original research summary & clinical findings

Background: Methotrexate (MTX), a folate-antagonist antimetabolite widely used in the management of malignancies, rheumatoid arthritis and psoriasis, has clinical utility that is frequently limited by dose-dependent hepatotoxicity driven largely by oxidative stress. Objective: This study was designed to comparatively evaluate the hepatoprotective potential of apigenin and alpha-tocopherol, individually and in combination, against MTX-induced hepatic injury in rats, with silymarin employed as the standard reference hepatoprotective agent. Methods: Twenty-four Wistar albino rats were allocated into six groups of four animals each: normal control; MTX control (20 mg/kg, i.p., single dose on day 7); silymarin (50 mg/kg/day, p.o.) plus MTX; apigenin (50 mg/kg/day, p.o.) plus MTX; alpha-tocopherol (100 mg/kg/day, p.o.) plus MTX; and a combination of apigenin and alpha-tocopherol plus MTX. Oral treatments were administered daily for fourteen days. Hepatic superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), together with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), were estimated, and liver sections were examined histologically. Results: MTX administration produced a marked depletion of hepatic SOD, CAT and GSH and a significant elevation of MDA, ALT, AST and ALP relative to the normal control (p<0.001), accompanied by hepatocellular degeneration, cytoplasmic vacuolation and pyknotic nuclei on histopathology. Pre-treatment with apigenin, alpha-tocopherol and, most markedly, their combination significantly attenuated these oxidative and biochemical derangements and preserved hepatic architecture (p<0.001 versus the MTX control), with the combined regimen producing the most consistent protection among the test groups and approaching the effect of silymarin. Conclusion: Apigenin and alpha-tocopherol confer hepatoprotection against methotrexate-induced liver injury through complementary antioxidant mechanisms, and their combined use may represent a rational adjunct strategy meriting further pharmacological and clinical investigation.