ABSTRACT
Experimental chronic kidney insufficiency (CKI; within 2-6 months) in rats, kept on a diet containing 0.6% Ca2+ and 0.6% P was accompanied by distinct azotemia, hyperphosphatemia, by a decrease in specific weight, in content of Ca2+, P and hydroxyproline in diaphyses as well as by a decrease in epiphyseal Ca2+. Daily administration of 0.025 micrograms of 1 alpha, 25-dihydroxy-cholecalciferol (1,25 (OH)2D3) into the animals did not normalize any of the patterns studied. At the same time, 1,25 (OH)2D3 increased the rate of hypercalciemia and demineralization of epiphyses, causing a slight hypercalciemia and increasing distinctly calcinosis of aorta as well as of the remaining part of the kidney. After daily administration of 24, 25-dihydroxycholecalciferol (24, 25 (OH)2D3) at a dose of 0.25 micrograms most of the patterns studied were normalized; specific weight, content of Ca2+ and P were increased in diaphyses simultaneously with a decrease in blood phosphorus concentration and in the level of azotemia. 24, 25 (OH)2D3 increased also the collagen content in diaphyses and epiphyses. The higher dose of 24, 25 (OH)2D3 (1.25 micrograms) did not exhibit higher effectivity. No one of the 24, 25 (OH)2D3 doses used did cause hypercalciemia and calcinosis. Combination of 0.025 micrograms 1,25 (OH)2D3 with 1.25 micrograms of 24, 25 (OH)2D3 decreased slightly the hypercalciemic, hyperphosphatemic and calcinosis inducing effects of 1,25 (OH)2D3 preventing completely the osteoporotic alterations in diaphyses but increasing the epiphysis demineralization; these results indicate that the doses of these metabolites must be decreased if their combination is required. The data obtained suggest that 24, 25 (OH)2D3 is a more effective and safe drug in correction of Ca2+-P metabolism impairments as well as of bone destruction under kidney insufficiency conditions as compared with 1,25 (OH)2D3.
Subject(s)
Bone and Bones/metabolism , Calcitriol/pharmacology , Calcium/metabolism , Dihydroxycholecalciferols/pharmacology , Kidney Failure, Chronic/metabolism , Kidney/metabolism , Phosphates/metabolism , 24,25-Dihydroxyvitamin D 3 , Animals , Bone and Bones/drug effects , Calcinosis/etiology , Calcinosis/metabolism , Disease Models, Animal , Kidney/drug effects , Male , RatsABSTRACT
A method for the synthesis of an analog of vitamin D3--1alpha-hydroxy vitamin D3 (1alpha-OH D3) from cholesta-4,6-dien-3beta-ol was developed. Biological activity of this compound in the chick organism was measured. The growth stimulating effect of 1alpha-OH D3 and its effect on bone tissue mineralization and serum biochemical parameters (content of calcium, inorganic phosphorus and activity of alkaline phosphatase) were 4--5 times higher than those of vitamin D3 in low doses (19.5--39 pmole/day). In chicks given 1alpha-OH D3 at doses of 39--195 pmole/day most biochemical parameters reached plateau typical of chicks adequately provided with vitamin D. A peculiar feature of 1alpha-OH D3 was a rapid response of the chick organism to/low doses. As early as one hour after intramuscular injection of 650 pmole of 1alpha-OH D3 to D-avitaminotic chicks, the content of calcium-bound protein in the intestinal mucosa and active transport of calcium ions in the inverted intestinal sac increased drastically. It was demonstrated that 1alpha-OH D3 showed antirachitic action, when the physiological reaction to vitamin D3 was inhibited by dietary strontium.
