Diosgenin mitigates oxidative stress and inflammation within the hepatorenal system associated with epilepsy and alcohol use disorders in murine models

The relationship between alcohol consumption, multiorgan dysfunction and seizures is still largely unexplored. Diosgenin is a naturally occurring phytosteroid with diverse therapeutic benefits. This study aimed to investigate the effects of diosgenin on liver and kidney (hepatorenal) oxidative stress following ethanol-exacerbated pentylenetetrazol-induced seizures. Adult mice were randomly divided into groups, and administered diosgenin (25 and 50 mg/kg, p.o.) or diazepam (3 mg/kg, p.o.) concurrently with maximal and sub-convulsive pentylenetetrazol-induced seizures from days 8–14, after first 7 days of binge ethanol (2 g/kg, oral gavage) administration. The influence of ethanol on pentylenetetrazol-induced seizures was determined in the liver and kidney tissues, along with oxidative stress and inflammatory enzyme markers. Ethanol-exacerbated pentylenetetrazol-induced seizures mediate a significant increase in hepatic and kidney levels of oxidative stress, evidenced by a reduced antioxidant system (glutathione, catalase, superoxide dismutase, glutathione-transferase) and increased lipid peroxidation, marked by elevated malondialdehyde concentration compared to control groups. This was also associated with increased myeloperoxidase activity, a marker of neutrophil infiltration, and increased liver, kidney, adrenal and adrenal weights. However, diosgenin increased the latency to seizures, increased glutathione, catalase, superoxide dismutase, and glutathione transferase levels in the mice. Diosgenin reduced liver and kidney oxidative stress and inflammation, suggesting protective effects in ethanol-exacerbated pentylenetetrazol-induced seizures.