Mitochondrial protection and anti-inflammatory effect of curcumin in inhibiting reproductive toxicity induced by sodium valproate in male mice

Abstract

Objective(s): Sodium valproate (VPA) has harmful effects on the male reproductive system. The present study aimed to investigate the influence of curcumin (CUR) in mitigating the VPA-induced reproductive toxicity in male mice.Materials and Methods: The male mice (mean weight 20 g and 8 weeks old) were divided into six groups (n=6): control, VPA only (500 mg/kg, IP), VPA plus different doses of CUR (25, 50, and 100 mg/kg, IP), CUR alone (100 mg/kg, IP). After treatment for eight consecutive weeks, the mice were sacrificed, testicle tissues were separated, and mitochondria were isolated with different centrifuge techniques. Various biomarkers were evaluated in testis tissue, including the concentration of lipid peroxidation, glutathione, protein carbonyl, nitric oxide, IL-6, and TNF-alpha. Also, mitochondrial toxicity, swelling, and membrane potential were assessed. Furthermore, sperm analysis and histopathological examination were done on testicular tissue.Results: VPA injection increased the amount of nitric oxide, inflammatory factors, mitochondrial toxicity, and oxidative stress markers (P<0.05). Also, histopathological and sperm analysis showed significant damage to testis tissue and a significant reduction in sperm count, motility, and normal morphology after VPA administration. CUR led to a substantial reduction of the inflammatory and oxidative stress parameters(P<0.05), restored the VPA-induced testis toxicity, and increased sperm count and motility (P<0.05).Conclusion: Our study demonstrates CUR's ameliorative effects on mitochondrial oxidative damage and inflammation caused by VPA-induced reproductive toxicity, which can be suggested as a strategy for reducing the side effects caused by VPA.