Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Environ Toxicol Pharmacol. 2013 Sep;36(2):274-283. doi: 10.1016/j.etap.2013.04.006. Epub 2013 Apr 23.
Aroclor 1254, a commercial mixture of highly toxic environmental pollutant, is known to cause testicular toxicity. The present study was undertaken to delineate and elucidate the nature and the mechanism of action of Aroclor 1254 on rat sperm in vitro. Sperm of adult rat were incubated with 10(-9)M, 10(-8)M or 10(-7)M of Aroclor 1254 for 3h. Sperm motility was significantly decreased. Moreover, sperm viability, acrosome reaction and mitochondrial membrane potential (Δψm) were significantly decreased in a dose-related pattern. DNA integrity was significantly decreased at 10(-8)M and 10(-7)M of Aroclor 1254, while it did not show any significant change at 10(-9)M. Aroclor 1254 induced downstream events included cytochrome c release and caspase-3 activation, in a dose-related manner. ATP content was decreased while protein carbonyl content was significantly increased in a dose-related manner. The oxidative stress status was also assessed. Hydrogen peroxide (H2O2) production and lipid peroxidation (LPO) were significantly increased in a dose-related pattern. The antioxidant enzymes SOD, CAT and GPx were significantly decreased, while at a concentration of 10(-9)M of Aroclor 1254, GR activity did not show any significant change. The non-enzymatic antioxidant (GSH) was significantly decreased in a dose-dependent manner. In conclusion; our data clearly show that Aroclor 1254 induces toxicity, oxidative stress and culminating in mitochondria mediated apoptosis in rat sperm.
Aroclor 1254 是一种具有高度毒性的环境污染物，已知会导致睾丸毒性。本研究旨在阐明 Aroclor 1254 在体外对大鼠精子的毒性作用及其机制。将成年大鼠的精子与 10(-9)M、10(-8)M 或 10(-7)M 的 Aroclor 1254 孵育 3 小时。精子的运动能力明显下降。此外，精子活力、顶体反应和线粒体膜电位（Δψm）呈剂量依赖性显著降低。只有在 10(-8)M 和 10(-7)M 的 Aroclor 1254 下，DNA 完整性才会显著降低，而在 10(-9)M 时则没有明显变化。Aroclor 1254 诱导的下游事件包括细胞色素 c 释放和 caspase-3 激活，呈剂量依赖性。ATP 含量下降，而蛋白羰基含量则呈剂量依赖性显著增加。氧化应激状态也进行了评估。H2O2 产生和脂质过氧化（LPO）均呈剂量依赖性显著增加。抗氧化酶 SOD、CAT 和 GPx 显著降低，而在 10(-9)M 的 Aroclor 1254 浓度下，GR 活性没有明显变化。非酶抗氧化剂（GSH）呈剂量依赖性显著降低。综上所述，我们的数据清楚地表明，Aroclor 1254 诱导大鼠精子毒性、氧化应激并最终导致线粒体介导的细胞凋亡。
