Carcinogenesis, Vol 18, 485-490, Copyright © 1997 by Oxford University Press
EM van Lieshout, DM Tiemessen, WH Peters and JB Jansen
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to
reduce cancer rates in oesophagus, stomach and colon of humans and animals.
Earlier, we showed that high human gastrointestinal tissue levels of
glutathione S-transferase (GST), a family of detoxification enzymes
consisting of class alpha, mu, pi and theta isoforms, were inversely
correlated with cancer risk. We investigated whether the NSAIDs
indomethacin, ibuprofen, piroxicam, acetyl salicylic acid (ASA), and
sulindac, 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 liver,
GST activity towards 1-chloro-2,4-dinitrobenzene was measured, GST isozyme
levels were determined by densitometrical analysis of Western blots after
immunodetection with monoclonal antibodies, and glutathione levels were
determined by HPLC. GST activity and GST mu levels were increased (1.2-1.8
x) in oesophagus and small intestine by indomethacin, ibuprofen, piroxicam
and sulindac. GST alpha levels were induced (1.2-2.8 x) in stomach by
piroxicam, in small intestine by indomethacin, ibuprofen, piroxicam and
sulindac, and in liver by piroxicam. GST pi levels were raised (1.9-3.6 x)
in stomach by ibuprofen, ASA, and sulindac, and in small intestine by
indomethacin, piroxicam, ASA, and sulindac. 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 efficient detoxification, may explain in part the
anticarcinogenic properties of NSAIDs.
ARTICLES
Effects of nonsteroidal anti-inflammatory drugs on glutathione S- transferases of the rat digestive tract
Department of Gastroenterology, University Hospital St Radboud, Nijmegen, The Netherlands.
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