1. The metabolic effects of p-aminophenol have been compared with those of paracetamol and other analgesics in studies of rat liver and kidney in vitro.
2. p-Aminophenol injected into rats inhibited gluconeogenesis from lactate in renal cortical tubules, but not in isolated hepatocytes, and reduced kidney ATP content without affecting the ATP content of liver. Perfused kidneys from rats previously injected with p-aminophenol showed a 50% reduction of ATP content, severe inhibition of Na+ reabsorption and reduction of inulin clearance without significant inhibition of gluconeogenesis from lactate.
3. Paracetamol, p-phenetidine, phenazone and aspirin, when given intravenously to rats, had no effect on renal tubular glucose synthesis from lactate or pyruvate. Paracetamol and aspirin both slightly inhibited renal glucose synthesis from several different substrates when added directly to tubules.
4. Paracetamol (4 mmol/l) inhibited glucose synthesis from lactate and other substrates by 50% or more in isolated hepatocytes. Glucose synthesis from lactate was inhibited 30% by concentrations of paracetamol as low as 0–5 mmol/l.
5. These results indicate that p-aminophenol is a potent inhibitor of proximal tubular function, with its main site of action the inhibition of ATP synthesis and energy production, and they confirm the primary hepatotoxic effect of paracetamol.