Hepatic handling of vitamin D3 in micronodular cirrhosis: a structure-function study in the rat.
The response to vitamin D3 (D3) was studied in a model of micronodular cirrhosis induced by CCl4. The uptake and C-25 hydroxylation of D3 were then studied in isolated-perfused liver preparations. CCl4-treated rats had a significantly lower fractional hepatic D3 uptake than controls; they also had lower 25-hydroxyvitamin D3 (25(OH)D3) concentrations in both liver and perfusate following 150 min of perfusion. CCl4 induced a wide spectrum of hepatic morphologic changes ranging from mild to large collagen infiltration, but micronodular cirrhosis was present in more than 90% of the animals. Histomorphometric analysis of the liver indicated an overall highly significant increase in the volume density (Vv) of collagen infiltration, and a reduction in the Vv normal hepatocytes following CCl4. Linear relationships were also observed between the Vv normal hepatocytes and the liver, perfusate, and total 25(OH)D3, while the 25(OH)D3 production decreased in a logarithmic fashion as the collagen infiltration of the liver parenchyma increased. These data show that the overall production of 25(OH)D3 is decreased in micronodular cirrhosis; they also indicate, however, that the D3-25 hydroxylase seems to stay unimpaired in the remaining hepatocytes of the diseased liver, and that the Vv normal hepatocytes constitute one of the major determinants of the 25(OH)D3 production by the cirrhotic rat liver.
Plourde
V
V
Centre de Recherche Clinique André-Viallet, Centre Hospitalier Saint Luc, Montréal, Québec, Canada.
Gascon-Barré
M
M
Coulombe
P A
PA
Vallières
S
S
Huet
P M
PM
D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D002762:Cholecalciferol / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014808:Vitamin D Deficiency / Q000378:metabolism*
D002762:Cholecalciferol; D002112:Calcifediol