NONSTEROIDAL ANTIINFLAMMATORY DRUGS ENHANCE GLUTATHIONE-S-TRANSFERASETHETA-LEVEL IN RAT COLON

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been claimed to red uce cancer rates in oesophagus, stomach and colon of humans and labora tory animals. Recently we showed that dietary administration of NSAIDs enhanced glutathione S-transferase (GST) class alpha, mu and pi level s in the upper part of the rat gastrointestinal tract, with minor effe cts in the colon. Enhancement of GSTs, a family of detoxification enzy mes consisting of class alpha, mu, pi and theta isoforms, might be one of the mechanisms leading to cancer prevention. The recently cloned G ST class theta levels have not yet been studied in this respect. We no w investigated whether the NSAIDs indomethacin, relafen, sulindac, ibu profen, piroxicam, and acetyl salicylic acid (ASA), incorporated indiv idually into the diet at 25, 200, 320, 400, 400 and 400 mg/kg, respect ively, affect gastrointestinal GSTT1-1 and GSTT2-2 levels in male Wist ar rats. GSTT1-1 and GSTT2-2 levels were determined in cytosolic fract ions of oesophagus, gastric, small intestinal and colonic mucosa and l iver by densitometrical analyses of Western blots after immunodetectio n with a monoclonal (GSTT1-1) or a polyclonal (GSTT2-2) antibody. Gast ric GSTT2-2 levels were induced by ibuprofen (1.6 X) and indomethacin (1.5 X), and colonic levels were induced by ASA (1.7 X). Colonic GSTT1 -1 levels were elevated by all NSAIDs tested except for relafen (1.5-6 .4 X). In conclusion, enhancement of colonic GSTT1-1 levels seems to b e a common working mechanism of NSAIDs. Enhanced enzyme activity, whic h may result from these higher GSTT1-1 levels, might lead to a more ef ficient detoxification of potential carcinogens and hence contribute t o the prevention of colon carcinogenesis. (C) 1998 Elsevier Science B. V. All rights reserved.