Hedera helix folium extract attenuates methotrexate-induced hepatotoxicity by modulating oxidative stress and inflammatory mediators

Methotrexate (MTX)-induced hepatotoxicity is linked to oxidative damage and inflammatory processes. Hedera helix folium (HHF) extract protects cells against oxidative damage. We investigated the role of HHF extract in tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10)-associated inflammation and oxidative stress in the pathology of MTX-associated liver injury in rats. Forty male rats were divided into one of five equal groups: Control, HHF, MTX, H₁₀₀+MTX and H₂₀₀+MTX. HHF extract was administered via the oral route at 100 mg/kg or 200 mg/kg once daily for seven days, while MTX was administered as a single dose of 20 mg/kg intraperitoneally. Intracardiac blood samples and liver tissue samples were collected at the conclusion of the experiment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased due to MTX. Increased ALT levels were significantly reduced by low-dose HHF and increased AST levels were significantly reduced by high-dose HHF administration. The application of MTX significantly increased malondialdehyde (MDA) and TNF-α levels, while significantly reducing those of glutathione (GSH) and IL-10. High-dose HHF also significantly lowered MDA and TNF-α levels, while significantly increasing those of GSH and IL-10. Histopathological damage findings observed due to MTX were significantly attenuated with high-dose HHF. In addition, the increased caspase-3, p53, and Bcl2 levels caused by MTX decreased with high-dose HHF administration. HHF extract can alleviate liver damage induced by MTX. This extract, which has the ability to reduce damage due to oxidative stress and inflammation, may represent an alternative approach to preventing MTX-induced liver damage.