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1. Liver and kidney glutathione are depleted in rats and mice following administration of N-hydroxyparacetamol. 2. Centrilobular hepatic necrosis and necrosis of renal proximal convoluted tubules were also found, the liver lesion predominantly in mice and the renal lesion predominantly in rats. Glutathione depletion was not responsible for this species difference. 3. These results indicate that N-hydroxyparacetamol is the metabolic precursor of the reactive toxic intermediate of paracetamol. They are also relevant to the pathogenesis of the renal damage associated with long term abuse of phenacetin containing compound analgesics.

1. p-Aminophenol, a known nephrotoxin, has been studied as a model for phenacetin-induced renal damage. 2. Respiration, oxidative phosphorylation and ATPase activity were inhibited in mitochondria isolated from the kidneys of treated rats; this could not be reversed by the addition of exogenous loosely bound cofactors and bovine serum albumin to the assay medium. 3. After treatment the mitochondrial levels of sodium and calcium were increased, potassium decreased and magnesium unaltered. 4. Mitochondria isolated from treated rats showed ultrastructural damage. 5. The results are interpreted to indicate that renal tubular cell mitochondrial injury is important in triggering cortical analgesic renal damage.

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