Hassoun Ezdihar A, Vodhanel Jennifer, Holden Bethany, Abushaban Ahmed
College of Pharmacy, University of Toledo, Toledo, Ohio 43606,, USA.
J Toxicol Environ Health A. 2006 Mar;69(5):381-93. doi: 10.1080/15287390500246431.
Ellagic acid (EA) and vitamin E succinate (VES) were previously shown to protect against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced reactive oxygen species (ROS) overproduction in certain brain regions of rats after subchronic exposure. The current study was designed to assess the modulation of antioxidant enzyme activities and glutathione (GSH) levels as protective measures for VES and EA against TCDD-induced ROS overproduction in four regions of rat brain. TCDD was administered to groups of rats at a daily dose of 46 ng/kg for 90 d. EA and VES were administered to some other groups of rats either alone or simultaneously with TCDD, every other day for 90 d. At the end of the treatment period, animals were sacrificed and brain regions were dissected, including cerebral cortex (Cc), hippocampus (H), cerebellum (C), and brainstem (Bs), for assay of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as GSH levels. While treatment of rats with VES alone or in combination with TCDD resulted in significant increases in SOD and CAT activities in different brain regions, treatment with EA resulted in a significant rise in total GSH levels and GSH-Px activity in those regions. Results may suggest antioxidant modulation by VES and EA as a mechanism for the previously observed protection by these compounds against TCDD-induced ROS overproduction in brain. Data also indicate there are two different pathways in the protection provided by the two antioxidants.
先前的研究表明,鞣花酸(EA)和维生素E琥珀酸酯(VES)可保护大鼠在亚慢性暴露后,其特定脑区免受2,3,7,8-四氯二苯并对二恶英(TCDD)诱导的活性氧(ROS)过量产生的影响。本研究旨在评估抗氧化酶活性和谷胱甘肽(GSH)水平的调节情况,作为VES和EA对TCDD诱导的大鼠脑四个区域ROS过量产生的保护措施。将TCDD以每日46 ng/kg的剂量给予大鼠组,持续90天。将EA和VES单独或与TCDD同时给予其他大鼠组,每隔一天给药一次,持续90天。在治疗期结束时,处死动物并解剖脑区,包括大脑皮层(Cc)、海马体(H)、小脑(C)和脑干(Bs),以测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活性以及GSH水平。单独用VES或与TCDD联合处理大鼠,导致不同脑区的SOD和CAT活性显著增加,而用EA处理则导致这些区域的总GSH水平和GSH-Px活性显著升高。结果可能表明VES和EA对抗氧化酶的调节作用是这些化合物先前观察到的对TCDD诱导的脑内ROS过量产生具有保护作用的机制。数据还表明,这两种抗氧化剂提供的保护存在两种不同的途径。