THE EFFECTS OF EXPERIMENTAL FASCIOLIASIS ON BILIRUBIN METABOLISM IN THE RAT

The effects of subclinical fasciolosis at various stages of its develo pment on bilirubin metabolism were investigated in rats. Studies were carried out at 3 (initial lesions), 6 (parenchymal degeneration), and 11 weeks (biliary localization of the parasite) after infection with a n oral dose of 20 metacercariae of Fasciola hepatica. Both bile flow a nd bile acid secretion were significantly reduced by Weeks 3 and 6 pos tinfection, while a significantly increased bile flow was found in the Ii-week group. Serum concentration of unconjugated bilirubin was elev ated at 3-6 weeks postinfection and that of conjugated bilirubin and t he esterified/total bilirubin ratio increased in all infected rats. Bi liary excretion of bilirubin mono- and diconjugates was maximally incr eased by 3-6 weeks, remaining elevated at 11 weeks. No significant cha nge in the biliary diconjugateimonoconjugate ratio was found in any of the groups. UDP-glucuronosyltransferase activity was reduced by Weeks 3 and 6. This was accompanied by a significantly lowered liver cytoch rome P450 concentration and an elevation in hepatic heme oxygenase act ivity. Blood hemoglobin concentration was significantly reduced and re ticulocyte count increased by 6 and 11 weeks. Our results indicate tha t enhanced bilirubin production, cholestasis, and a reduced conjugatin g activity could be responsible for the changes in plasma and bile pig ment composition during the acute stage of fasciolosis. Hemolysis and a high bilirubin excretion are maintained when the parasite migrates i nto the biliary ducts. (C) 1994 Academic Press, Inc.