Liver and Kidney Damage Induced by N-Hydroxyparacetamol

K. Healey Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

I. C. Calder Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

A. C. Yong Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

C. A. Crowe Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

C. C. Funder Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

K. N. Ham Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

J. D. Tange Departments of Chemistry and Pathology, University of Melbourne, Parkville, Victoria, 3052, Australia

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Abstract

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.

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Liver and Kidney Damage Induced by N-Hydroxyparacetamol

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Liver and Kidney Damage Induced by N-Hydroxyparacetamol

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