Kim Danil, Yamagishi Norio, Abe Izumi, Furuhama Kazuhisa, Devkota Bhuminand, Ohashi Shuichi
United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
J Vet Med Sci. 2011 Feb;73(2):185-91. doi: 10.1292/jvms.10-0306. Epub 2010 Sep 22.
The present study evaluated the effects of calcitriol dissolved in an oleaginous vehicle (calcitriol-OLE) on changes in plasma calcitriol, calcium and bone metabolic markers in nonpregnant, nonlactating Holstein cows. Five cows were treated intramuscularly or subcutaneously with calcitriol-OLE and oleaginous vehicle alone using a 5 × 5 Latin square design. Additionally, cows were also treated intravenously with calcitriol dissolved in an aqueous vehicle (calcitriol-AQU) for comparison. The plasma calcitriol concentrations after intramuscular and subcutaneous calcitriol-OLE administrations peaked at 24 and 12 hr, respectively, remained significantly elevated until day 3, returned to the respective control levels on day 5 and decreased significantly on day 7. In cows given intravenous calcitriol-AQU, the calcitriol levels decreased with linearity on day 1. The plasma calcium levels rose from 12 hr post-dose and peaked on day 2 for both preparations and in all three administration routes. Significantly increased calcium levels continued until day 5 in the intramuscular and intravenous routes and day 7 in the subcutaneous route. The plasma osteocalcin concentrations significantly increased from day 3 for calcitriol-OLE and from day 5 for calcitriol-AQU, whereas the bone resorption markers, tartrate-resistant acid phosphatase isoform 5b and hydroxyproline, decreased during this time. These results suggest that either intramuscular or subcutaneous injection of calcitriol-OLE extends and maintains supraphysiological calcitriol levels in the plasma and prolongs hypercalcemia. Moreover, exogenous calcitriol in normocalcemic cows increases the plasma osteocalcin concentration and decreases the plasma levels of bone resorption markers probably due to hypercalcemia.
本研究评估了溶解于油性载体中的骨化三醇(骨化三醇 - OLE)对非妊娠、非泌乳荷斯坦奶牛血浆骨化三醇、钙及骨代谢标志物变化的影响。采用5×5拉丁方设计,对5头奶牛分别进行肌肉注射或皮下注射骨化三醇 - OLE以及单独注射油性载体处理。此外,为作比较,还对奶牛静脉注射溶解于水性载体中的骨化三醇(骨化三醇 - AQU)。肌肉注射和皮下注射骨化三醇 - OLE后,血浆骨化三醇浓度分别在24小时和12小时达到峰值,直至第3天仍显著升高,第5天恢复至各自对照水平,第7天显著下降。静脉注射骨化三醇 - AQU的奶牛,骨化三醇水平在第1天呈线性下降。两种制剂经所有三种给药途径给药后,血浆钙水平均在给药后12小时开始上升,并在第2天达到峰值。肌肉注射和静脉注射途径的血钙水平在第5天前持续显著升高,皮下注射途径则在第7天前持续显著升高。骨化三醇 - OLE组血浆骨钙素浓度从第3天开始显著升高,骨化三醇 - AQU组从第5天开始显著升高,而在此期间骨吸收标志物抗酒石酸酸性磷酸酶同工型5b和羟脯氨酸水平下降。这些结果表明,肌肉注射或皮下注射骨化三醇 - OLE可延长并维持血浆中骨化三醇的超生理水平,并延长高钙血症状态。此外,正常血钙水平奶牛体内的外源性骨化三醇可能由于高钙血症而导致血浆骨钙素浓度升高,骨吸收标志物血浆水平下降。