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硫辛酸减轻成年大鼠中Aroclor 1260诱导的肝毒性。

Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

作者信息

Aly Hamdy A A, Mansour Ahmed M, Hassan Memy H, Abd-Ellah Mohamed F

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.

出版信息

Environ Toxicol. 2016 Aug;31(8):913-22. doi: 10.1002/tox.22101. Epub 2014 Dec 23.

Abstract

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

摘要

本研究旨在探讨多氯联苯混合物1260(Aroclor 1260)诱导肝毒性的机制以及硫辛酸对其的保护作用。成年雄性白化大鼠被分为六组。第一组作为对照组。第二组给予硫辛酸(35毫克/千克/天)。分别以20、40或60毫克/千克/天的剂量通过灌胃法给大鼠服用Aroclor 1260(第三、四、五组)。第六组在给予Aroclor 1260(40毫克/千克/天)前24小时用硫辛酸(35毫克/千克/天)进行预处理。所有组的治疗持续15天。血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、碱性磷酸酶和乳酸脱氢酶活性以及总胆红素、总胆固醇和甘油三酯显著升高,而总蛋白、总白蛋白和高密度脂蛋白显著降低。肝脏中过氧化氢生成和脂质过氧化显著增加,而超氧化物歧化酶和过氧化氢酶活性以及还原型谷胱甘肽(GSH)含量显著降低。肝脏中半胱天冬酶-3和-9活性显著增加。硫辛酸预处理使所有这些异常情况显著恢复至正常水平。总之,Aroclor 1260至少部分通过诱导氧化应激导致肝功能障碍。肝细胞的凋亡作用参与了Aroclor 1260诱导的肝损伤。硫辛酸可以保护大鼠免受Aroclor 1260诱导的肝毒性。©2014威利期刊公司。《环境毒理学》31: 913 - 922,2016。

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