THE INFLUENCE OF METABOLIC VARIATION ON ANALGESIC NEPHROTOXICITY - EXPERIMENTS WITH THE GUNN RAT

The analgesics aspirin and paracetamol, administered as single i.v. doses, produced renal lesions in the homozygous Gunn rat. The lesions affected both cortex and medulla but were less severe than the renal lesions of analgesic nephropathy. By contrast, the reactive compounds p-aminophenol and 5-aminosalicylic acid, which cause renal damage in other less susceptible strains, produce cortical and medullary renal lesions, respectively, 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 may be partly due to impaired glucuronide formation and consequent delayed excretion of nephrotoxic substances.