Protection of rats against the hepatotoxic effect of paracetamol.

In view of increasing knowledge of the mechanism of production of hepatic damage by paracetamol, and the results of recent studies suggesting a beneficial effect from cysteamine administered soon after an overdose, studies were carried out in the rat on a number of possibly protective agents, using oral paracetamol in a dose of 2·5 g/kg body weight. Histological evidence of liver damage was reproducibly obtained with corresponding reductions in the levels of cytochrome P450. This was completely prevented by prior oral administration of cysteamine in a dose of 300 mg/kg body weight. The levels of cytochrome P450 were also maintained following an intraperitoneal injection of α-tocopherol (400 mg/kg body weight) but the effect on the histological evidence of liver damage was less. The administration of glutathione, propranolol and thioctic acid did not prevent the liver damage, although with these agents—except glutathione—the number of wedge shaped areas of necrosis (infarcts) in the liver was reduced.