EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON GLUTATHIONE S-TRANSFERASES OF THE RAT DIGESTIVE-TRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated t o reduce cancer rates in oesophagus, stomach and colon of humans and a nimals. Earlier, we showed that high human gastrointestinal tissue lev els of glutathione S-transferase (GST), a family of detoxification enz ymes consisting of class alpha, mu, pi and theta isoforms, were invers ely correlated with cancer risk. We investigated whether the NSAIDs in domethacin, ibuprofen, piroxicam, acetyl salicylic acid (ASA), and sul indac, supplemented in the diet for 2 weeks at 25, 400, 400, 400, and 320 ppm, respectively, influenced gastrointestinal GSTs in male Wistar rats. In cytosolic fractions of oesophagus, stomach, intestine and li ver, GST activity towards 1-chloro-2,4-dinitrobenzene was measured, GS T isozyme levels were determined by densitometrical analysis of Wester n blots after immunodetection with monoclonal antibodies, and glutathi one levels were determined by HPLC. GST activity and GST mu levels wer e increased (1.2-1.8 x) in oesophagus and small intestine by indometha cin, ibuprofen, piroxicam and sulindac. GST alpha levels were induced (1.2-2.8 x) in stomach by piroxicam, in small intestine by indomethaci n, ibuprofen, piroxicam and sulindac, and in Liver by piroxicam. GST p i levels were raised (1.9-3.6 x) in stomach by ibuprofen, ASA, and sul indac, and in small intestine by indomethacin, piroxicam, ASA, and sul indac. Glutathione levels were raised (1.2-2.3 x) by indomethacin and ASA in small intestine and by piroxicam in oesophagus. Enhancement of GSTs in the upper part of the digestive tract, resulting in a more eff icient detoxification, may explain in part the anticarcinogenic proper ties of NSAIDs.