Effects of nonsteroidal anti-inflammatory drugs on glutathione S- transferases of the rat digestive tract

Autor: W.H.M. Peters, J.B.M.J. Jansen, Dorien M. Tiemessen, E.M.M. van Lieshout
Rok vydání: 1997
Předmět:
Male
Cancer Research
Indomethacin
Ibuprofen
Pharmacology
Piroxicam
Substrate Specificity
Nutrition
secretion and motility
chemistry.chemical_compound
Cytosol
Esophagus
Sulindac
Indometacin
Voeding
secretie en motoriek
medicine
Animals
Anticarcinogenic Agents
Rats
Wistar
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Glutathione Transferase
Gastrointestinal tract
Aspirin
Dose-Response Relationship
Drug
biology
Stomach
Anti-Inflammatory Agents
Non-Steroidal
Voeding en premaligne aandoeningen
Nutrition and premalignant diseases
General Medicine
Glutathione
digestive system diseases
Small intestine
Rats
Intestines
Isoenzymes
medicine.anatomical_structure
Glutathione S-transferase
Liver
chemistry
Organ Specificity
Enzyme Induction
biology.protein
Digestive System
medicine.drug
Zdroj: Carcinogenesis
Carcinogenesis, 18, 3, pp. 485-490
Carcinogenesis, 18, 485-490
ISSN: 1460-2180
0143-3334
DOI: 10.1093/carcin/18.3.485
Popis: 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.
Databáze: OpenAIRE
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