Effect of non-steroidal anti-inflammatory drugs and the pro-carcinogen 1,2 dimethylhydrazine on the rat intestinal membrane structure and function.
The present study was designed to evaluate the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal biochemical composition, function and histology during 1, 2-dimethylhydrazine (DMH) administration. Sprague Dawley male rats were divided into five different groups viz: Group 1 (control, vehicle treated), Group 2 (DMH-treated, 30 mg/kg body weight/week in 1 mM EDTA-saline, 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). After six weeks of treatment, brush border membrane was isolated from the jejunum segment of all the groups and changes in the associated enzymes such as sucrase, lactase, maltase, alkaline phosphatase, membrane lipid composition, fluorescence polarizations of diphenylhexatriene, pyrene excimer formation, histological changes and surface characteristics were studied. The results indicated a significant alteration in the enzyme activity as well as changes in the structure and function of the intestine in the presence of the pro-carcinogen, DMH, which suggests the possible chemopreventive efficacy of NSAIDs against the intestinal cancer.
Mittal
N
N
Department of Biophysics, Panjah University, Chandigarh, India.
Kanwar
S Singh
SS
Sanyal
S Nath
SN
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000494:pharmacology*; D032761:Animal Experimentation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000077613:Etoricoxib; D005454:Fluorescence Polarization; D007413:Intestinal Mucosa / Q000187:drug effects*; D007414:Intestinal Neoplasms / Q000517:prevention & control; D007421:Intestine, Small / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D008563:Membrane Lipids; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; D019813:1,2-Dimethylhydrazine; D000068579:Celecoxib; D001241:Aspirin; D000077613:Etoricoxib