Mittal Neha, Kanwar Shailender Singh, Sanyal Sankar Nath
Department of Biophysics, Panjab University, Chandigarh, India.
Int J Toxicol. 2008 Mar-Apr;27(2):169-74. doi: 10.1080/10915810801977880.
The present study was designed to evaluate the effects of three nonsteroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal antioxidant enzyme status and surface characteristics during 1,2-dimethylhydrazine (DMH) administration. Male Sprague-Dawley rats were divided into five different groups: Group 1 (control, vehicle treated); group 2 (DMH treated, 30 mg/kg body weight/week, subcutaneously); group 3 (DMH + aspirin 60 mg/kg body weight); group 4 (DMH + celecoxib 6 mg/kg body weight); group 5 (DMH + etoricoxib 0.64 mg/kg body weight). Postmitochondrial fraction were isolated from the intestinal segments and different oxidative parameters and other parameters studied, such as the lipid peroxides, reduced and total glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, nitric oxide, citrulline, and nucleic acids. At the end of 6 weeks of treatment, the results indicated a significant alteration in the antioxidative defense status of the intestine in the presence of the procarcinogen DMH, which was restored with the administration of NSAIDs. The study, therefore, suggests a possible mechanism for the chemopreventive effects of NSAIDs against the experimental intestinal cancer in rats.
本研究旨在评估三种具有不同环氧化酶选择性的非甾体抗炎药（NSAIDs）对1,2 - 二甲基肼（DMH）给药期间小肠抗氧化酶状态和表面特征的影响。雄性Sprague - Dawley大鼠被分为五个不同的组：第1组（对照组，给予赋形剂）；第2组（给予DMH，30 mg/kg体重/周，皮下注射）；第3组（DMH + 阿司匹林60 mg/kg体重）；第4组（DMH + 塞来昔布6 mg/kg体重）；第5组（DMH + 依托考昔0.64 mg/kg体重）。从肠段分离出线粒体后组分，并研究不同的氧化参数和其他参数，如脂质过氧化物、还原型和总谷胱甘肽、超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽S - 转移酶、一氧化氮、瓜氨酸和核酸。在治疗6周结束时，结果表明在致癌物前体DMH存在的情况下，小肠的抗氧化防御状态发生了显著改变，而给予NSAIDs后这种改变得以恢复。因此，该研究提示了NSAIDs对大鼠实验性肠癌具有化学预防作用的一种可能机制。
