Copper protects against galactosamine-induced hepatitis.

Summary Although copper is believed to be hepatotoxic in Wilson's disease and Indian Childhood Cirrhosis (ICC), the rat shows only minimal hepatic damage on copper-loading. To investigate the possibility that copper deposition may potentiate the effects of a superimposed hepatitis, d-galactosamine (GalN) was given to copper-loaded and control rats. In the non-copper-dosed rats, GalN 0.85 g/kg i.p. produced elevated serum AST (3731 ± 545 IU/l; normal 64.8 ± 2.1), ALT (2090 ± 190 IU/l; normal 18.0 ± 0.7), and OCT (16.7 ± 2.6 mmol/min/ml; normal 0.12 ± 0), and liver cell necrosis with portal infiltration. In rats whose liver copper was elevated to 1298 ± 169 μg/g (control 18.7 ± 1.7) by oral copper supplementation, GalN produced much smaller increases in AST (825 ± 122 IU/l), ALT (103 ± 15 IU/l) and OCT (0.27 ± 0.02 mmol/min/ml) and minimal histological damage. Viable bacterial cell counts from faecal homogenates showed that the anaerobically cultured bacteria were reduced on copper-dosing of rats. Therefore the protective effect of copper may be due to a decrease in gut-derived endotoxin acting on the liver, or to an impaired prostaglandin synthesis or perhaps to synthesis of acute phase reactants.