a review of methotrexate-induced hepatic and renal injuries: oxidative stress as the main reason

Methotrexate (mtx) has various side effects, including hepatotoxicity, renal injury, gastrointestinal distress, and neurological toxicity. oxidative stress (os) and mitochondrial dysfunction may contribute to hepatotoxicity, but there is no direct evidence of their effect on renal injury. understanding these relationships could help researchers develop preventative measures and improve therapeutic uses of mtx. this review emphasized os as the leading cause of mtx-induced hepatic and renal injuries. mtx induces os in the liver, evidenced by increased malondialdehyde levels and decreased total antioxidant capacity. this oxidative stress leads to lipid peroxidation, a key factor in mtx toxicity, causing elevated liver enzymes, cell membrane damage, and necrosis. mtx also increases reactive oxygen species (ros) and decreases hepatocellular glutathione which is known as a natural endogenous antioxidant, further contributing to cellular apoptosis and death. antioxidants have been identified as potential mitigators of lipid peroxidation, protecting cellular proteins and maintaining defense mechanisms. additionally, mtx decreased nadph, leading to reduced glutathione levels and impaired antioxidant defenses. renal impairment associated with mtx is indicated by altered creatinine, bun, electrolyte levels, and uric acid, linked to decreased renal mitochondrial function and increased kidney ros and lipid peroxidation. this suggests that oxidative stress and mitochondrial toxicity are key mechanisms in mtx-induced nephrotoxicity. mtx, a common treatment for immune-mediated diseases like rheumatoid arthritis, has been linked to adverse effects on cells due to its oxidative stress. this decrease in tissue antioxidant capacity may alter cell membrane integrity and cause other injuries. the use of antioxidants may have some benefits for the adverse effects associated with mtx in some patients.