Vinpocetine Mitigates Methotrexate-Induced Liver Injury in Rats Through Modulating Intercellular Communication

Methotrexate (MTX) has been widely implemented in managing several malignancies, inflammatory conditions such as rheumatic arthritis, and autoimmune illnesses. Hepatotoxicity is a significant side effect of MTX, characterized by increased oxidative stress (OS) and inflammation. Vinpocetine (Vinpo) is a prescription medication with a favorable safety profile. It exerts anti-inflammatory and oxidant implications that might be novel candidates for protecting against MTX-induced hepatotoxicity. This study investigates the therapeutic impact of Vinpo against MTX-stimulated liver damage via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Rats are allocated into three groups: (1) the Control (saline); (2) the MTX-control (20 mg/kg; injected once i.p.), and (3) the Vinpo + MTX groups. Vinpo was administered orally for 7 days, during which MTX was given intraperitoneally once at the end of Day 3. The liver functions, OS markers, inflammatory mediators, Nrf2, HO-1, NF-κB, and apoptotic signals were estimated. Vinpo lead to enhancement in superoxide dismutase (SOD) enzyme activity, elevation in glutathione (GSH), and a hindrance in malondialdehyde (MDA). It also enhances Nrf2 and HO-1, inhibiting NF-κB (p65) expression and apoptotic markers. Moreover, Vinpo therapy, in conjunction with MTX, restores the normal histological structure of hepatic tissues. Our data suggested that Vinpo exerts a preventive effect against MTX-induced toxicity through anti-oxidative, anti-inflammatory, and apoptotic activities, mediated via Nrf2/HO-1/Nf-κB and caspase-3/Bax/Bcl-2 pathways.