Shaneh Moein, Chahardori Milad, Talebpour Amiri Fereshte, Amani Nahid, Shaki Fatemeh
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Basic Med Sci. 2025;28(8):1027-1036. doi: 10.22038/ijbms.2025.82254.17791.
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.
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.
VPA injection increased the amount of nitric oxide, inflammatory factors, mitochondrial toxicity, and oxidative stress markers (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(0.05), restored the VPA-induced testis toxicity, and increased sperm count and motility (0.05).
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.
丙戊酸钠(VPA)对雄性生殖系统有有害影响。本研究旨在探讨姜黄素(CUR)对减轻VPA诱导的雄性小鼠生殖毒性的影响。
将雄性小鼠(平均体重20g,8周龄)分为六组(n = 6):对照组、仅VPA组(500mg/kg,腹腔注射)、VPA加不同剂量CUR组(25、50和100mg/kg,腹腔注射)、单独CUR组(100mg/kg,腹腔注射)。连续治疗八周后,处死小鼠,分离睾丸组织,并用不同的离心技术分离线粒体。在睾丸组织中评估各种生物标志物,包括脂质过氧化、谷胱甘肽、蛋白质羰基、一氧化氮、IL-6和TNF-α的浓度。此外,评估线粒体毒性、肿胀和膜电位。此外,对睾丸组织进行精子分析和组织病理学检查。
注射VPA增加了一氧化氮、炎症因子、线粒体毒性和氧化应激标志物的量(P<0.05)。此外,组织病理学和精子分析显示,给予VPA后睾丸组织有明显损伤,精子数量、活力和正常形态显著降低。CUR导致炎症和氧化应激参数大幅降低(P<0.05),恢复了VPA诱导的睾丸毒性,并增加了精子数量和活力(P<0.05)。
我们的研究证明了CUR对VPA诱导的生殖毒性引起的线粒体氧化损伤和炎症具有改善作用,这可被认为是减少VPA引起的副作用的一种策略。