Copper protects against galactosamine-induced hepatitis.
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 micrograms/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.
Barrow
L
L
Department of Child Health, University of Leicester, U.K.
Kantarjian
A
A
Tanner
M S
MS
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D003300:Copper / Q000494:pharmacology*; D005243:Feces / Q000382:microbiology; D005688:Galactosamine / Q000037:antagonists & inhibitors*; D009954:Ornithine Carbamoyltransferase / Q000097:blood
D005688:Galactosamine; D003300:Copper; D009954:Ornithine Carbamoyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase