Exploring phytotherapeutic approach in the management of valproic acid-induced toxicity

The antiepileptic drug, valproic acid (VPA), also used for treating psychiatric disorders, is hampered by its toxicity. Its associated adverse effects include hepatotoxicity, nephrotoxicity, central nervous system (CNS) depression, respiratory failure, acute pancreatitis, thrombocytopenia, hyperammonaemia, bone marrow suppression, and teratogenicity. Currently, no antidotes exist for treating VPA toxicity and therapeutic management is majorly supportive while modifying drug disposition. The lack of effective treatment has prompted evaluating plant-derived products to manage this challenge since studies show their protective potential against drug-induced toxicities. This review investigates purported mechanisms and the protective capacity of plants products against VPA-induced toxicity. The compiled studies revealed that VPA causes hepatotoxicity, nephrotoxicity, ocular toxicity, teratogenicity and reproductive toxicity among others. Further findings highlighted the oxido-inflammatory and apoptotic pathway as crucial mechanisms of VPA-induced organ toxicities. Extracts of Apium graveolens L., Bacopa monniera, Green tea, Kaempferia parviflora, Korean red ginseng, Ocimum sanctum, Oryza sativa, Withania somnifera and plant-derived compounds, including diammonium glycyrrhizinate, sulforaphane, vitamin U, B6, E, diallyl trisulfide, curcumin, α-tocopherol, quercetin, piperine, resveratrol, hesperitin, thymoquinone, caffeic acid and asiatic acid exhibited protection against VPA-induced toxicities. From these observations, it is suggested that further studies should target evaluating more plant products as well as identifying and isolating specific compounds from such, and others demonstrating protective effect against toxicities induced by VPA.