Phytoconstituents as therapeutic agents in combating methotrexate-induced hepatotoxicity and nephrotoxicity.

INTRODUCTION: Methotrexate (MTX) is a type of disease-modifying antirheumatic drug and one of the most effective anticancer agents in clinical practices. However, hepatotoxicity and nephrotoxicity are common side effects associated with MTX therapy. Complementary natural medicines for treating hepatorenal toxicity have received widespread research interest. AREA COVERED: Plant-based natural products have shown promise in managing organ toxicities caused by various drugs. These natural products possess medicinal properties that can be used as a complementary therapy to counteract MTX-induced hepatotoxicity and nephrotoxicity. This study comprehensively reviewed the research on natural products like berberine, gallic acid, resveratrol, etc. that show potential in moderating MTX-induced hepatotoxicity and nephrotoxicity in preclinical models. We explored Google Scholar, Scopus, and PubMed for studies on plant-based natural products and their protective actions against MTX-induced hepatotoxicity and nephrotoxicity. This updated report can be very valuable in deveoping phytotherapeutics for effectively managing the toxicities associated with MTX therapy. EXPERT OPINION: The studied evidence underscores the promising potential of phytochemicals in mitigating MTX-induced hepatotoxicity and nephrotoxicity via different mechanisms. Given the extensive usage of MTX in various diseases, additional clinical studies are critical to further authenticate these results and optimize phytotherapeutic approaches for enhancing the safety and efficacy of treatment.