Basic and prophylactic study on the toxicity of endocrine disruptors and lifestyle Testicular injury by di-(2-ethylhexyl) phthalate

邻苯二甲酸二（2-乙基己基）酯（DEHP）是聚氯乙烯（PVC）等塑料最常见的增塑剂，但被怀疑是内分泌干扰物。最近的研究表明DEHP对雄性生殖器官的毒性作用，如成熟和生长阶段的大鼠睾丸损伤，这种损伤可能是由于邻苯二甲酸单-（2-乙基己基）酯（MEHP）诱导的氧化应激所致。由于含DEHP的PVC广泛用于制造消费品、食品容器、玩具和医疗器械，DEHP污染广泛存在，一般人群在食物、水和空气中接触到DEHP，这引起了对人类生殖危害的关注。在本研究中，为了阐明广泛存在于食品和饮料中的化学物质对DEHP睾丸毒性的影响，我们将维生素E和C、咖啡因、烟酸和乙醇等抗氧化剂与DEHP一起给予生长阶段的大鼠。在4或5周龄的SD大鼠中，给予1-2% DEHP饮食1-2周，睾丸萎缩并伴有精子发生。幼年大鼠对DEHP的睾丸毒性更敏感。血液或睾丸MEHP浓度与dehp引起的睾丸萎缩程度存在相关性，提示MEHP作为活性毒物的剂量与睾丸损伤之间存在剂量效应关系。在4周龄大鼠中，给予含有2% DEHP的饮食和补充维生素E和C的水，睾丸萎缩明显受到抑制。在含有1% DEHP的4周龄大鼠饮食中，添加咖啡因（0.05w/w%）、烟酸（0.5 w/w%）或乙醇（2.5或5 v/v%）的水也能防止睾丸萎缩。这些抗氧化剂的作用机制尚不清楚。然而，我们的研究结果表明，抗氧化活性和自由基清除能力参与抑制DEHP诱导的睾丸损伤。

Di-(2-ethylhexyl) phthalate (DEHP) is the most common plasticizer for plastics such as polyvinyl chloride (PVC) but suspected to be an endocrine disruptor. Recent studies have shown the toxic effects of DEHP on male reproductive organs such as testicular injury in rats in both mature and growth stages, and this injury has been suggested to be due to oxidative stress induced by mono-(2-ethylhexyl) phthalate (MEHP). Since PVC containing DEHP is widely used in manufacturing consumer goods, food containers, toys, and medical instruments, DEHP contamination is widespread, and the general population is exposed to DEHP in food, water, and air, which arouses concern about human reproductive hazards.In this study, to clarify the effects of chemical substances widely distributed in foods and beverages on the testicular toxicity of DEHP, we administered antioxidants such as vitamins E and C, caffeine, nicotinic acid, and ethanol together with DEHP to rats in the growth stage. In 4- or 5-week-old SD rats given a 1-2% DEHP containing diet for 1-2 weeks, testicular atrophy accompanied by a spermatogenesis developed. Young rats were more susceptible to the testicular toxicity of DEHP. There was a correlation between the blood or testicular MEHP concentration and the degree of DEHP-induced testicular atrophy, suggesting a dose-effect relationship between the dose of MEHP as an active toxicant and testicular injury.In 4-week-old rats given a 2% DEHP containing diet and water supplemented with vitamins E and C, testicular atrophy was definitely inhibited. Water supplemented with caffeine (0.05w/w%), nicotinic acid (0.5 w/w%), or ethanol (2.5 or 5 v/v%) also prevented testicular atrophy in 4-week-old rats given a 1% DEHP containing diet. The action mechanism of these antioxidants was unclear. However, our results suggest the involvement of antioxidant activity and free radical scavenging capacity in the inhibition of DEHP induced testicular injury.