Research Laboratories 2, Fuji Yakuhin Co., Ltd., Saitama, Saitama Prefecture, Japan.
Tokyo Headquarters, Fuji Yakuhin Co., Ltd., Chiyoda-ku, Tokyo Prefecture, Japan.
J Pharm Pharmacol. 2021 Jun 8;73(7):947-955. doi: 10.1093/jpp/rgab019.
Ectopic calcification such as vascular calcification, involves the formation of calciprotein particle (CPP), that is, colloidal particle of calcium phosphate bound to serum protein. In this study, a novel parameter for CPP formation was introduced, thereby the effect of FYB-931, a bisphosphonate compound was evaluated.
CPP formation in rat serum was assessed by the area under the curve (AUC) of the change in absorbance over time, and the commonly used T50, as indices. In vivo, the rats were treated with vitamin D3 to induce vascular calcification and then intravenously administered FYB-931 or etidronate thrice weekly for 2 weeks.
In vitro, FYB-931 was the most potent inhibitor of CPP formation and it also inhibited the maximum response of CPP formation at higher concentrations. The AUC of the change in absorbance provided obvious dose-dependency, while T50 did not. FYB-931 dose-dependently prevented aortic calcification in vivo as well as CPP formation ex vivo more potently than etidronate. AUC showed a stronger correlation with the degree of aortic calcification than T50.
The AUC in CPP formation can be an alternative parameter that reflects calcification. Based on the findings, FYB-931 has potential as an anti-calcifying agent.
血管钙化等异位钙化涉及钙磷蛋白颗粒（CPP）的形成，即与血清蛋白结合的磷酸钙胶体颗粒。本研究引入了 CPP 形成的新参数，从而评估了双膦酸盐化合物 FYB-931 的作用。
通过吸光度随时间变化的曲线下面积（AUC）评估大鼠血清中 CPP 的形成，并使用常用的 T50 作为指标。体内，用维生素 D3 处理大鼠以诱导血管钙化，然后每周静脉注射 FYB-931 或依替膦酸三次，共 2 周。
体外，FYB-931 是 CPP 形成的最有效抑制剂，在较高浓度下也抑制 CPP 形成的最大反应。吸光度变化的 AUC 呈明显的剂量依赖性，而 T50 则没有。FYB-931 可剂量依赖性地预防体内主动脉钙化和 CPP 形成，其效力强于依替膦酸。AUC 与主动脉钙化程度的相关性强于 T50。
CPP 形成中的 AUC 可以作为反映钙化的替代参数。基于这些发现，FYB-931 具有作为抗钙化剂的潜力。
