Assessment of calciprotein particle formation by AUC of the absorbance change: effect of FYB-931, a novel bisphosphonate compound
| Autor: | Seiichi Kobashi, Naoki Ashizawa, Ishida Koichi, Takashi Iwanaga, Shota Morikane, Naoki Kurita |
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| Rok vydání: | 2020 |
| Předmět: |
Vitamin
Calcium Phosphates Calcium-Regulating Hormones and Agents 030232 urology & nephrology Pharmaceutical Science chemistry.chemical_element 030204 cardiovascular system & hematology Calcium Pharmacology 03 medical and health sciences Ectopic calcification chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Colloids Vascular Calcification Diphosphonates Dose-Response Relationship Drug Chemistry Area under the curve Etidronic Acid medicine.disease In vitro Rats Treatment Outcome Area Under Curve Ex vivo Calcification |
| Zdroj: | The Journal of pharmacy and pharmacology. 73(7) |
| ISSN: | 2042-7158 |
| Popis: | Objective 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. Methods 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. Key findings 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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