Generation of drug metabolite antigenicity in the intestinal mucosa.
Both nitroreductase and transglutaminase activities have been assayed in the 10,000 X g supernatant fluids of rat intestine homogenates after Triton X-100 treatment. Incubation of 14C-nitrofurantoin in the intestine extract yielded protein-bound 14C-labeled products. Injection into rabbits of the conjugated protein similarly prepared with unlabeled nitrofurantoin elicited formation of antibodies against nitrofurantoin. These results suggest that intestinal metabolism and conjugation to protein of orally administered drugs may serve as a probable mechanism of drug allergy, and this may be accomplished by enzymatic coupling of relatively stable drug metabolites to protein carriers.
D000818:Animals; D000941:Antigens; D002250:Carbon Radioisotopes; D002432:Cecum / Q000201:enzymology; D003902:Detergents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology*; D007421:Intestine, Small / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009582:Nitrofurantoin / Q000378:metabolism*; D009601:Nitroreductases / Q000378:metabolism*; D017830:Octoxynol; D010088:Oxidoreductases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013501:Surface-Active Agents / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism*
D000941:Antigens; D002250:Carbon Radioisotopes; D003902:Detergents; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D017830:Octoxynol; D009582:Nitrofurantoin; D010088:Oxidoreductases; D009601:Nitroreductases; D011503:Transglutaminases