Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey.
Toxicol Mech Methods. 2012 Jul;22(6):415-23. doi: 10.3109/15376516.2012.666652. Epub 2012 Mar 15.
This study was designed to examine the oxidative stress potential of di(2-ethylhexyl)phthalate (DEHP) on rat kidney and to evaluate possible protective effect of selenium (Se) status. Se deficiency (SeD) was produced in 3-week old Sprague-Dawley rats by feeding them ≤ 0.05 Se mg/kg diet for 5 weeks; Se supplementation group (SeS) 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 total glutathione (GSH), thiols and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP treatment was found to induce oxidative stress in rat kidney, as evidenced by significant decreases in GPx1 (20%) and SOD (30%) activities and GSH levels (20%), along with marked decrease in thiol content (40%) and increase in TBARS (~30%) levels. The effects of DEHP was more pronounced in SeD rats, whereas Se supplementation was protective by providing substantial elevations of GPx1 and GPx4 activities and GSH levels. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting renal tissue from the oxidant stressor activity of DEHP.
本研究旨在探讨邻苯二甲酸二（2-乙基己基）酯（DEHP）对大鼠肾脏的氧化应激潜力，并评估硒（Se）状态的可能保护作用。通过给 3 周龄的 Sprague-Dawley 大鼠喂食含硒量≤0.05mg/kg 的饮食 5 周，制造出 Se 缺乏（SeD）；Se 补充组（SeS）喂食含 1mg Se/kg 的饮食。在喂养期的最后 10 天，通过灌胃给 DEHP 处理组大鼠给予 1000mg/kg 的剂量。测量抗氧化硒酶[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；总谷胱甘肽（GSH）、巯基和硫代巴比妥酸反应物质（TBARS）的浓度。DEHP 处理导致大鼠肾脏发生氧化应激，这表现为 GPx1（约 20%）和 SOD（约 30%）活性以及 GSH 水平（约 20%）显著降低，同时硫醇含量（约 40%）明显减少，TBARS（约 30%）水平显著升高。在 SeD 大鼠中，DEHP 的作用更为明显，而 Se 补充则具有保护作用，可显著提高 GPx1 和 GPx4 活性以及 GSH 水平。这些发现强调了 Se 作为有效氧化还原调节剂的关键作用，以及 Se 状态在保护肾脏组织免受 DEHP 氧化剂应激活性方面的重要性。
