Antinecrotic effect of 3-palmitoyl-(+)-catechin against liver damage induced by galactosamine or ethanol in the rat.

The antinecrotic potential of a new drug, 3-palmitoyl-(+)-catechin (PC), which is a derivative of (+)-cyanidanol-3, was studied in two different experimental models of necrosis of the liver in the rat: acute hepatitis induced by galactosamine and liver damage induced by a combination of chronic ethanol feeding and hypoxia. The extent of liver damage was assessed by histological examination and by measuring blood hepatic enzyme and bilirubin levels. Intraperitoneal and oral treatments with PC were carried out at different dosages and times, before acute galactosamine intoxication. PC treatment decreased the extent of diffuse necrosis and inflammation in liver tissue and reduced galactosamine-induced biochemical deterioration. The lowest active doses of PC were 25 mg/kg, i.p. and 500 mg/kg by mouth. In experiments with ethanol, we confirmed that a 6-h period of hypoxia produced necrosis of the liver in rats undergoing chronic treatment with ethanol. Simultaneous treatment with PC (80 mg/kg/day) for 21 days during ethanol feeding gave significant protection against histological and biochemical deterioration induced by ethanol and hypoxia. The anti-necrotic effect of PC in two models, which are recognized as producing part of the biochemical and/or histological deterioration induced by viruses and ethanol in man, indicates that it is a potentially useful agent for the treatment of necrosis of the human liver.