Metabolism and nephrotoxicity of phenacetin and sulfanilamide.
The mechanisms of renal damage produced by sulfanilamide and phenacetin were studied. N-Hydroxyphenacetin, 4-hydroxylaminobenzenesulfonamide (4-HABSA) and p-aminophenol were established to be nephrotoxic metabolites. As well as N-hydroxylase activity of sulfanilamide, that of phenacetin in kidney microsomes of rats was increased about 4 times by pretreatment with 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) which is a potent inducer of cytochrome P-448. Parallel to this enzyme induction, pretreatment with PenCB enhanced the nephrotoxicity of phenacetin and sulfanilamide in rats. On the other hand, the formation of p-aminophenol from phenacetin was also confirmed in rat kidney in vitro. These results suggested that 4-HABSA, N-hydroxyphenacetin and p-aminophenol formed in kidney play an important role in the renal damage produced by sulfanilamide and phenacetin.
D000818:Animals; D006900:Hydroxylation; D007668:Kidney / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D010615:Phenacetin / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000378:metabolism / Q000633:toxicity*
D013424:Sulfanilamides; D000077145:Sulfanilamide; D010615:Phenacetin