title: Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver.
abstract: The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.
authors.affiliation: Tokyo Research and Development Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Furuhama
authors.forename: K
authors.initials: K
authors.lastname: Yabe
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D002796:Choline Deficiency / Q000473:pathology / Q000503:physiopathology; D000242:Cyclic AMP / Q000097:blood; D004195:Disease Models, Animal; D005001:Ethionine / Q000494:pharmacology; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D005693:Galactosemias; D005934:Glucagon / Q000494:pharmacology; D006207:Half-Life; D006498:Hepatectomy; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002791:Cholesterol, Dietary; D010743:Phospholipids; D005934:Glucagon; D002784:Cholesterol; D000242:Cyclic AMP; D007208:Indocyanine Green; D005001:Ethionine