Nonsteroidal anti-inflammatory drugs enhance glutathione S-transferase Theta levels in rat colon

Esther M.M. Van Lieshout, Dorien M. Tiemessen, Hennie M.J. Roelofs, Wilbert H.M. Peters

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24 Citations (Scopus)

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been claimed to reduce cancer rates in oesophagus, stomach and colon of humans and laboratory animals. Recently we showed that dietary administration of NSAIDs enhanced glutathione S-transferase (GST) class alpha, mu and pi levels in the upper part of the rat gastrointestinal tract, with minor effects in the colon. Enhancement of GSTs, a family of detoxification enzymes consisting of class alpha, mu, pi and theta isoforms, might be one of the mechanisms leading to cancer prevention. The recently cloned GST class theta levels have not yet been studied in this respect. We now investigated whether the NSAIDs indomethacin, relafen, sulindac, ibuprofen, piroxicam, and acetyl salicylic acid (ASA), incorporated individually into the diet at 25, 200, 320, 400, 400 and 400 mg/kg, respectively, affect gastrointestinal GSTT1-1 and GSTT2-2 levels in male Wistar rats. GSTT1-1 and GSTT2-2 levels were determined in cytosolic fractions of oesophagus, gastric, small intestinal and colonic mucosa and liver by densitometrical analyses of Western blots after immunodetection with a monoclonal (GSTT1-1) or a polyclonal (GSTT2-2) antibody. Gastric GSTT2-2 levels were induced by ibuprofen (1.6×) and indomethacin (1.5×), and colonic levels were induced by ASA (1.7×). Colonic GSTT1-1 levels were elevated by all NSAIDs tested except for relafen (1.5–6.4×). In conclusion, enhancement of colonic GSTT1-1 levels seems to be a common working mechanism of NSAIDs. Enhanced enzyme activity, which may result from these higher GSTT1-1 levels, might lead to a more efficient detoxification of potential carcinogens and hence contribute to the prevention of colon carcinogenesis.
Original languageEnglish
Pages (from-to)305-311
JournalBiochimica et Biophysica Acta - General Subjects
Volume1381
Issue number3
DOIs
Publication statusPublished - 24 Aug 1998
Externally publishedYes

Bibliographical note

Acknowledgements
This work was supported by grant KUN 94-715 from the Dutch Cancer Society (E.M.M.v.L.).

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