Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey.
Environ Toxicol. 2014 Jan;29(1):98-107. doi: 10.1002/tox.20776. Epub 2011 Oct 5.
Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3-weeks-old Sprague-Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ∼18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是最广泛使用的增塑剂，本研究旨在探讨氧化应激是否是其睾丸毒性的潜在机制之一。由于硒（Se）已知在睾丸中发挥关键作用并调节细胞内氧化还原平衡，因此本研究进一步评估了 Se 状态对 DEHP 毒性的影响。通过对 3 周龄 Sprague-Dawley 大鼠进行为期 5 周的饮食中 Se 含量≤0.05mg/kg 的处理来诱导 Se 缺乏，Se 补充组则给予 1mg/kg 的饮食。DEHP 处理组在喂养期的最后 10 天通过灌胃给予 1000mg/kg 的 DEHP 剂量。测定抗氧化硒酶[谷胱甘肽过氧化物酶 1（GPx1）、谷胱甘肽过氧化物酶 4（GPx4）、硫氧还蛋白还原酶（TrxR）]、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽 S-转移酶（GST）的活性；还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）的浓度以及 GSH/GSSG 氧化还原比；以及硫代巴比妥酸反应物（TBARS）的水平。结果表明，DEHP 诱导了大鼠睾丸的氧化应激，这表现为 GSH/GSSG 氧化还原比显著降低（>10 倍），TBARS 水平显著增加，并且在 Se 缺乏大鼠中更为明显，GSH/GSSG 氧化还原比降低了约 18.5 倍，GPx4 活性显著降低，而 Se 补充则通过提供氧化还原比的大幅升高和减少脂质过氧化起到了保护作用。这些发现强调了 Se 作为一种有效的氧化还原调节剂的关键作用以及 Se 状态在保护睾丸组织免受 DEHP 氧化应激的重要性。
