Kinetic analysis of 25-hydroxyvitamin D3 metabolism in strontium-induced rickets in the chick.

Abstract

A B S T R A C T Kinetic data analysis was used to derive a six-compartment computer model which describes the in vivo [3H]25-hydroxyvitamin D3 ([3H]25-OHD3) metabolism in control and strontium rachitic chicks. Plasma concentrations of 25-OHD3 (13 pmol/ml) and 24, 25-dihydroxyvitamin D3 (0.9 pmol/ml) were 18 and 125% greater than controls, respectively, whereas the corresponding level for la,25-dihydroxyvitamin D3 (0.3 pmol/ml) was only 30% of control. Plasma disappearance of 25-OHD3 was fitted using a two-compartment model in which the metabolite extrapolated half-life was nearly twice as large for strontium rachitic chicks (71 compared to 41 h). Intestinal sequestration of la,25-dihydroxyvitamin D3 was assumed to be irreversible and was fitted by a single exponential term in which metabolite uptake rate and tissue concentration in strontium rickets was suppressed to 20 and 10% of control, respectively. In contrast, uptake of 25-OHD3 by the intestine was observed to occur by a reversible process in which metabolite concentration was 45% greater in the strontium rachitic compared to control group. The developed compartment model accepts time-dependent control or perturbed metabolite data for the plasma and (or) intestinal pools and provides quantitative values for metabolite pool size, flux rate, and turnover time.

Kinetics of Intravenously Administered 25-Hydroxyvitamin D3 in Sheep and the Effect of Exposure to Ultraviolet Radiation

“…However, the 20-d post-injection concentration of 250HD3 was still higher than the pre-injection concentration. The present results on plasma disappearance pattern of [3HI 250HD 3 in wethers are similar to these observed in chicks that were administered iv [3H] 250HD 3 (Omdahl et al 1977). The data from that study on [3H] 250HD 3 plasma disappearance were fitted to a two-compartment model, and defined the liphasic curve, consisting of rapid and slow disappearance phases.…”

The effects of stable strontium on calcium metabolism.: II. Effects of 1α-hydroxyvitamin D3 in strontium-fed rats, and inhibitory effect of strontium on bone resorptionin vitro

“…First, it strontium causes hepatic or biliary dysfunction, the intestinal absorption of la (OH)D3 will be impaired. Second, serum Sr ~+ acts together with Ca ~+ to trigger an increase in the 24-hydroxylation [16] of la (OH) D3. Despite the fact that serum 1,25 (OH)2D level in the Sr-a group almost recovered to that in the Co-D group, the intestinal calcium absorption in the Sr-a group was still suppressed, as compared with that in the Co-D group, and no significant difference was observed between the Sr-D and Sr-a groups.…”

Interactive effects of vitamin D3 and strontium on performance, nutrient retention and bone mineral composition in laying hens

“…With respect to intestinal absorption, like Ca the transfer of Sr across the intestinal epithelial layer is due in part to the calcium binding protein calbindin, which is controlled by D 3 . At very high doses Sr has been shown to disrupt the hydroxylation of 25‐hydroxyvitamin D 3 (25‐OHD 3 ) to the active hormone 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in the kidneys, severely reducing calbindin synthesis in the intestine, with subsequent reduction in Ca absorption …”