Effect of nonsteroidal anti-inflammatory drugs and the procarcinogen 1,2-dimethylhydrazine on the antioxidant defense system.
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.
Mittal
Neha
N
Department of Biophysics, Panjab University, Chandigarh, India.
Kanwar
Shailender Singh
SS
Sanyal
Sankar Nath
SN
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002273:Carcinogens; D009569:Nitric Oxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005978:Glutathione; D019813:1,2-Dimethylhydrazine