Effects of acute carbon tetrachloride poisoning on vitamin D₃ metabolism in the rat

Abstract

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.