[Comparative study of the toxicity of 1 alpha-hydroxyvitamin D3 and 24,25 (RS)-dihydroxyvitamin D3 in rats].
The toxic effects of 1 alpha (OH)D3 and 24,25 (OH)2D3 administered in doses of 0.25, 2.5 and 25 micrograms per animal a day were compared in rats weighing initially 230-260 g and fed an artificial diet containing 0.65 and 0.50% of Ca and P, respectively. After 5 days of administering different doses of 1 alpha (OH) D3 hypercalcemia and hyperphosphatemia developed whatever the dose, the animals' weight and density of the osseous tissue dropped starting with a dose of 2.5 micrograms, together with a high death rate and Ca accumulation by soft tissues at a dose of 25 micrograms per animal. Unlike 1 alpha (OH)D3, 24,25 (OH)2D3 did not exert any hypercalcemic or hyperphosphatemic action when given in a high dose (25 micrograms). On the contrary, it promote the decrease of the Ca and P blood levels. 24,25 (OH)2D3 did not bring about Ca accumulation by the organs or reduction of the osseous tissue density whatever the dose applied. In addition, the metabolite administered in a dose of 25 micrograms arrested the animals' growth. Thus, when given in comparable doses (the physiologic requirement of 1 alpha (OH)D3 and 24,25 (OH)2D3 for rats are 0.025 and 0.25 micrograms/day, respectively), 24,25 (OH)2D3 was at least one order of magnitude less active as regards its capacity to increase the Ca and P blood levels and to resorb the osseous tissue. The data obtained and the inhibitory effect on the growth of the 100-fold dose of 24,25 (OH)2D3 point to the feasibility of the short-term use of the metabolite in doses that do not exceed more than 10-fold the physiologic dose.
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001862:Bone Resorption / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006887:Hydroxycholecalciferols / Q000633:toxicity*; D006934:Hypercalcemia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010758:Phosphorus; D015650:24,25-Dihydroxyvitamin D 3; D002118:Calcium; C008088:alfacalcidol
Sravnitel'noe izuchenie toksichnosti 1 al'fa-oksivitimina D3 i 24,25 (RS)-dioksivitamina D3 u krys.