AN ANIMAL-MODEL FOR COPPER-ASSOCIATED CIRRHOSIS IN INFANCY

In Indian childhood cirrhosis (ICC) and related disorders of infancy, hepatic copper overload is associated with cirrhosis, Since copper adm inistration alone has not been shown to induce cirrhosis in animals, s ynergy between copper and a second hepatotoxin has been suggested. Thi s study investigates the ability of long-term exposure to copper and a pyrrolizidine alkaloid, retrorsine, to produce a model of copper-asso ciated cirrhosis in rats. Groups of rat pups suckled on mothers fed 25 mg/kg diet retrorsine were weaned onto a diet containing 0.5 g/kg die t copper and retrorsine in varying dosage for 13 weeks. Histological s imilarities between the human disease and rats given copper with retro rsine 5 mg/kg diet included parenchymal destruction, fibrosis, nodular regeneration, and copper accumulation, There were significant histolo gical differences from the human disorder, possibly attributable to in ter-species variability or the critical timing or duration of exposure to hepatotoxins in the neonatal period, The hypothesis that ICC resul ts from copper and a second hepatotoxin has not been disproved, (C) 19 98 John Wiley & Sons, Ltd.