CYTOTOXICITY OF BENZO[C]PHENANTHRIDINIUM ALKALOIDS IN ISOLATED RAT HEPATOCYTES

Sanguinarine, chelerythrine and fagaronine were examined for hepatotox ic effect. Administration of sanguinarine and chelerythrine (10 mg/kg/ day; i.p.) produced marked parenchymal injury not found in the livers of fagaronine treated rats. In chronic administration of sanguinarine (0.2 mg/kg/56 days; i.p.) degeneration and necrosis were not observed in the liver. The effect of the alkaloids was tested by enzyme leakage (LDH and ASAT) and changes in glutathione levels in isolated rat hepa tocytes. Sanguinarine produced the greatest toxicity followed by lesse r toxicity in the case of chelerythrine while no toxicity was displaye d with fagaronine. These effects correlate with pK(R+) values for pseu dobase formation. Finally, no increased lipid peroxidation or mitochon drial membrane damage were found.