Razi Drug Research Center, 440827Iran University of Medical Sciences, Tehran, Iran.
Medicinal Plant Research Center, 48407Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221078867. doi: 10.1177/09603271221078867.
Di-(2-ethylhexyl) phthalate (DEHP) is a well-known endocrine-disrupting compound inducing degeneration of testes. Gallic acid (GA) is a polyphenol with various pharmacological properties, including antioxidant and anti-inflammatory effects. This research evaluated effects of different doses of GA on DEHP-induced testicular injury in adult mice. Male mice were randomly divided into five groups and treated with agents for two weeks; group (I) received normal saline and corn oil (5 mL/kg/day, p. o.), group (II) received DEHP (2 g/kg/day, dissolved in corn oil, p. o.), groups (III, IV, and V) received DEHP + GA (25, 50, and 100 mg/kg/day, p. o.). Body and testes weights, serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were evaluated. The number of sperms and sperm motility and viability were analyzed in the cauda epididymis. Histological changes, oxidative/nitrosative stress markers, and inflammatory cytokines levels were examined in testes. Body and testes weights, the number of spermatogonia, primary spermatocyte and early spermatid, and late spermatid and sperm vitality, and progressive motility were significantly reduced in mice exposed to DEHP. Serum testosterone level decreased and serum LH and FSH levels increased in DEHP-exposed mice. These alterations were associated with the increased oxidative stress level and inflammatory responses in testicular tissue. Treatment with GA (50 and 100 mg/kg/day) attenuated DEHP-induced alterations in oxidative stress markers and inflammatory cytokines and reversed abnormality in sperm characteristic and number, tissue structure, and serum hormones levels. Results indicated that GA might be a promising agent against male gonadal toxicity induced by endocrine disrupting chemicals including DEHP.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种众所周知的内分泌干扰化合物，可诱导睾丸退化。没食子酸（GA）是一种具有多种药理作用的多酚，包括抗氧化和抗炎作用。本研究评估了不同剂量 GA 对成年小鼠 DEHP 诱导的睾丸损伤的影响。雄性小鼠随机分为五组，并用药物处理两周；第（I）组给予生理盐水和玉米油（5 mL/kg/天，口服），第（II）组给予 DEHP（2 g/kg/天，溶于玉米油，口服），第（III、IV 和 V）组给予 DEHP+GA（25、50 和 100 mg/kg/天，口服）。评估了体重和睾丸重量、血清睾酮、黄体生成素（LH）和卵泡刺激素（FSH）水平。在附睾尾部分析精子数量、精子活力和活力。检查睾丸的组织学变化、氧化/硝化应激标志物和炎症细胞因子水平。暴露于 DEHP 的小鼠的体重和睾丸重量、精原细胞、初级精母细胞和早期精子细胞以及晚期精子和精子活力以及前向运动精子的数量显著减少。暴露于 DEHP 的小鼠的血清睾酮水平降低，血清 LH 和 FSH 水平升高。这些改变与睾丸组织中氧化应激水平和炎症反应的增加有关。GA（50 和 100 mg/kg/天）治疗可减轻 DEHP 诱导的氧化应激标志物和炎症细胞因子的改变，并逆转精子特征和数量、组织结构和血清激素水平的异常。结果表明，GA 可能是一种有前途的对抗包括 DEHP 在内的内分泌干扰化学物质引起的男性性腺毒性的药物。
