The increase in skin 7-dehydrocholesterol induced by an hypocholesterolemic agent is associated with elevated 25-hydroxyvitamin D3 plasma level

Abstract

Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N'-(2-chlorophenyl)-N-piperazinyl-1- [propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05 +/- 0.20; HCG 917, 0.3 mg/kg: 1.41 +/- 0.22; HCG 917, 5.0 mg/kg: 2.35 +/- 0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2 +/- 2.2; HCG 917 5.0 mg/kg: 57.6 +/- 6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism.