Avti Pramod Kumar, Kumar Surender, Pathak Chander Mohan, Vaiphei Kim, Khanduja Krishan Lal
Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India.
Toxicol Sci. 2006 Feb;89(2):547-53. doi: 10.1093/toxsci/kfj041. Epub 2005 Nov 9.
The present study was designed to evaluate the effects of long-term use of aqueous extract of gutkha (a form of smokeless tobacco) on the antioxidant defense status and histopathological changes in liver, lung, and kidney of male Wistar rats. Animals were orally administered aqueous extract of smokeless tobacco (AEST) at a low dose (96 mg/kg body weight per day) for 2 and 32 weeks, and at a high dose (960 mg/kg body weight per day) for 2 weeks. High-dose AEST for 2 weeks decreased the hepatic glutathione (GSH) and glutathione peroxidase (GPx), and increased lipid peroxidation (Lpx) by 17%, 19%, and 20%, respectively. Low-dose AEST for 32 weeks significantly decreased (p < 0.05) the antioxidant status in these organs. In liver, AEST decreased GSH levels and the activities of superoxide dismutase (SOD), catalase (CAT), and GPx by 34.6%, 29%, 17.1%, and 17.4%, respectively, but it increased Lpx by 64%. In kidney, GSH, SOD, CAT, and GPx were decreased by 26.6%, 23%, 33%, and 18%, respectively, with an increase of Lpx by 65%. AEST decreased the lung GSH, SOD, CAT, and GPx, and increased lung Lpx by 43%, 28.5%, 37%, 40%, and 24%, respectively. However, no change in the plasma levels of vitamins A, C, and E were observed with AEST treatment. Histopathological findings suggest that administration of AEST at the high dose for 2 weeks or at the low dose for 32 weeks could cause mild to moderate inflammation in liver and lungs. In conclusion, a decrease in the antioxidant defense system and long-term inflammation caused by smokeless tobacco may be risk factors for gutkha-induced pathogenesis.
本研究旨在评估长期使用古特卡（一种无烟烟草形式）水提取物对雄性Wistar大鼠肝脏、肺和肾脏抗氧化防御状态及组织病理学变化的影响。动物分别以低剂量（每天96毫克/千克体重）口服无烟烟草水提取物（AEST）2周和32周，以及高剂量（每天960毫克/千克体重）口服2周。高剂量AEST处理2周使肝脏谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPx）降低，脂质过氧化（Lpx）分别增加17%、19%和20%。低剂量AEST处理32周显著降低（p<0.05）这些器官的抗氧化状态。在肝脏中，AEST使GSH水平以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和GPx的活性分别降低34.6%、29%、17.1%和17.4%，但使Lpx增加64%。在肾脏中，GSH、SOD、CAT和GPx分别降低26.6%、23%、33%和18%，Lpx增加65%。AEST使肺组织中GSH、SOD、CAT和GPx降低，肺组织Lpx分别增加43%、28.5%、37%、40%和24%。然而，AEST处理未观察到血浆中维生素A、C和E水平的变化。组织病理学结果表明，高剂量AEST处理2周或低剂量AEST处理32周可导致肝脏和肺部轻度至中度炎症。总之，无烟烟草引起的抗氧化防御系统下降和长期炎症可能是古特卡诱导发病机制的危险因素。
