The influence of metabolic variation on analgesic nephrotoxicity. Experiments with the Gunn rat.
The analgesics aspirin and paracetamol administered as single I.V. doses produce renal lesions in the homozygous Gunn rat. The lesions affect both cortex and medulla but are less severe than the renal lesions of analgesic nephropathy. By contrast the reactive compounds p-aminophenol and 5-aminosalicylic acid which are known to cause renal damage in other less susceptible strains respectively produce cortical and medullary renal lesions in homozygous Gunn rats which are as extensive as those found in patients with analgesic nephropathy. The increased frequency of renal lesions from the analgesics aspirin and paracetamol as compared to heterozygous and albino rats and the increased severity of the lesions due to p-aminophenol and 5-aminosalicylic acid is considered to be at least partly due to impaired glucuronide formation and consequent delayed excretion of nephrotoxic substances.
D000082:Acetaminophen / Q000009:adverse effects / Q000378:metabolism; D000627:Aminophenols / Q000009:adverse effects / Q000378:metabolism; D000636:Aminosalicylic Acids / Q000009:adverse effects / Q000378:metabolism; D000700:Analgesics / Q000009:adverse effects* / Q000378:metabolism*; D000818:Animals; D001241:Aspirin / Q000009:adverse effects / Q000378:metabolism; D006580:Genetic Carrier Screening; D006720:Homozygote; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019804:Mesalamine; D051381:Rats; D011911:Rats, Gunn / Q000378:metabolism*; D011922:Rats, Mutant Strains / Q000378:metabolism*
D000627:Aminophenols; D000636:Aminosalicylic Acids; D000700:Analgesics; D000082:Acetaminophen; D019804:Mesalamine; D001241:Aspirin