Faculty of Pharmacy, Department of Toxicology, Hacettepe University, Ankara, Turkey.
Drug Chem Toxicol. 2011 Oct;34(4):379-89. doi: 10.3109/01480545.2010.547499. Epub 2011 Jun 30.
Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate (DEHP) is the most widely used derivative in various consumer products and medical devices. Animal studies show that DEHP and various other phthalates cause reproductive and developmental toxicity. Although the evidences are limited, it seems reasonable that DEHP may have a potential for similar adverse effects in humans. Such concerns are increasing, particularly for the developing reproductive system of male infants and children. By taking into account the essentiality of selenium (Se) in testicular structure and functions and the high prevalence of inadequate Se intake in various part of the world, this study was designed to investigate the testicular toxicity of DEHP in Se-deficient male rats and to examine the possible preventive effects of Se supplementation on phthalate toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats with a ≤0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during the last 10 days of the feeding period. Testicular histopathology, sperm count and motility, and sperm morphology were examined, and plasma levels of sex hormones were measured. Toxicity and antiandrogenic effects of DEHP were evidenced by disturbed testicular histology and spermatogenesis, diminished testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and sperm motility. The effects of DEHP were much more pronounced in Se-deficient rats, whereas Se supplementation was found to be protective, reflecting its regulating role in cellular redox equilibrium.
邻苯二甲酸酯是大量生产的增塑剂,而邻苯二甲酸二(2-乙基己基)酯(DEHP)是各种消费品和医疗器械中使用最广泛的衍生物。动物研究表明,DEHP 和各种其他邻苯二甲酸酯会导致生殖和发育毒性。尽管证据有限,但 DEHP 似乎有可能对人类产生类似的不良影响。这种担忧正在增加,特别是对男性婴儿和儿童发育中的生殖系统。考虑到硒(Se)在睾丸结构和功能中的重要性,以及世界上许多地方硒摄入不足的高发率,本研究旨在研究 DEHP 在硒缺乏雄性大鼠中的睾丸毒性,并研究硒补充对邻苯二甲酸酯毒性的可能预防作用。通过用含硒量≤0.05mg/kg 的饮食喂养 3 周龄的 Sprague-Dawley 大鼠 5 周来产生硒缺乏。补充组喂食 1mg Se/kg 的饮食,DEHP 处理组在喂养期的最后 10 天通过灌胃接受 1000mg/kg 的剂量。检查了睾丸组织病理学、精子计数和活力以及精子形态,并测量了血浆性激素水平。DEHP 的毒性和抗雄激素作用表现为睾丸组织学和精子发生紊乱、睾丸激素、促黄体生成素(LH)和促卵泡激素(FSH)水平降低以及精子活力降低。在硒缺乏的大鼠中,DEHP 的影响更为明显,而硒补充被发现具有保护作用,反映了其在细胞氧化还原平衡中的调节作用。