cholecalciferol and Carbon-Tetrachloride-Poisoning

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.

Topics: Animals; Calcifediol; Carbon Tetrachloride Poisoning; Cholecalciferol; In Vitro Techniques; Kinetics; Liver; Liver Cirrhosis; Male; Rats; Rats, Inbred Strains; Reference Values; Vitamin D Deficiency

To achieve biologic potency, vitamin D must undergo two successive hydroxylations, first, in the liver and then, in the kidney. Carbon tetrachloride is known to cause extensive damage to the liver, but its effect on vitamin D metabolism has not been studied thoroughly. The effect of carbon tetrachloride on renal hydroxylation of 25-hydroxyvitamin D3 has not been studied. To evaluate the acute effect of carbon tetrachloride on vitamin D metabolism in the liver, vitamin D depleted rats received a single intraperitoneal injection of carbon tetrachloride (2.0 mL/kg body weight). After 24 h, they were given 55, 550, or 5050 pmol [3H]vitamin D3 intravenously. Twenty-four hours after injection of [3H]vitamin D3, aliquots of serum and liver were analyzed for [3H]vitamin D3 and its metabolites by high performance liquid chromatography. Sera of carbon tetrachloride treated rats had higher [3H]vitamin D3 and [3H]25-hydroxyvitamin D and lower [3H]1,25-dihydroxyvitamin D3 concentrations than did control sera. Livers of carbon tetrachloride treated rats contained more [3H]vitamin D3, [3H]25-hydroxyvitamin D3, and more fat. Liver histology showed massive centrilobular necrosis in the treated rats. Thus, our experiment in rats given an acute dose of carbon tetrachloride provided no evidence of impairment of vitamin D metabolism by the liver, but offered a suggestion that 25-hydroxyvitamin D3 metabolism by the kidney might be impaired. To determine the acute effect of carbon tetrachloride on metabolism of vitamin D3 by the kidney, we studied hydroxylation of [3H]25-hydroxyvitamin D3 in isolated perfused kidney. Kidneys from the treated rats showed a 66% reduction in [3H]1,25-dihydroxyvitamin D3 production.

Topics: Animals; Calcifediol; Calcitriol; Carbon Tetrachloride Poisoning; Cholecalciferol; Kidney; Male; Rats

Female rats treated with D-galactosamine showed increased serum enzyme levels of lactate dehydrogenase, alanine transaminase and sorbitol dehydrogenase as well as moderately elevated liver calcium and decreased potassium contents 4 and 8 hours after drug administration. Slightly but significantly more calcium was sequestered in the liver when the animals were additionally pretreated with vitamin D3, while the other investigated factors were not altered by this treatment. A different pattern was found in carbon-tetrachloride-induced liver lesion. Liver calcium levels were also raised when animals with carbon tetrachloride were pretreated with vitamin D3, but in contrast to D-galactosamine injury, liver enzyme release and electrolyte shift were markedly inhibited under these conditions. Together with previously reported results these findings support our concept that an early rise in liver cell calcium content with a related protective effect is a specific phenomenon in carbon-tetrachloride-induced liver cell damage.

Topics: Alanine Transaminase; Animals; Calcium; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholecalciferol; Female; Galactosamine; L-Iditol 2-Dehydrogenase; L-Lactate Dehydrogenase; Liver; Potassium; Rats

Topics: Alanine Transaminase; Animals; Calcium; Carbon Tetrachloride Poisoning; Cholecalciferol; Female; Histocytochemistry; L-Lactate Dehydrogenase; Liver; Magnesium; Rats