CN-121987610-A - Application of BAPTA-AM in preparation of medicines for improving dental fluorosis

Abstract

The invention provides an application of BAPTa-aM in preparing a medicament for improving dental fluorosis, wherein BAPTa-aM is used for preparing the medicament for improving dental fluorosis. The BAPTa-aM of the invention can promote normal mineralization of enamel by correcting the calcium steady state of the glazed cells and reversing the mitochondrial damage induced by sodium fluoride, thereby providing a brand new candidate substance and a definite action target point for the drug treatment of the fluospot teeth.

Inventors

• LV YING
• WANG YANG
• HU YONG
• WANG ZHOUZHOU
• YANG JIALING
• LI YONG

Assignees

• 贵州医科大学

Dates

Publication Date

20260508

Application Date

20260403

Claims (4)

1. 1. An application of BAPTA-AM in preparing a medicament for improving dental fluorosis, which is characterized in that the BAPTA-AM has a structural formula as follows: ; the BAPTA-AM is used for preparing medicines for improving the dental fluorosis.
2. 2. Use of BAPTA-AM in the manufacture of a medicament for improving dental fluorosis according to claim 1 wherein the use comprises one or more of the following: The BAPTA-AM is used for improving the imbalance of the calcium ion homeostasis in LS8 cells induced by excessive sodium fluoride; the BAPTA-AM is used to ameliorate excessive sodium fluoride induced mitochondrial damage to LS8 cells.
3. 3. Use of BAPTA-AM according to claim 2 in the manufacture of a medicament for improving dental fluorosis, wherein said BAPTA-AM is capable of reducing the intracellular calcium ion concentration of LS8 and promoting calcium ion efflux when said BAPTA-AM is used to improve an excess sodium fluoride-induced imbalance in LS8 intracellular calcium ion homeostasis.
4. 4. Use of BAPTA-AM according to claim 2 for the manufacture of a medicament for ameliorating dental fluorosis, wherein said BAPTA-AM is used to ameliorate excessive sodium fluoride-induced mitochondrial damage in LS8 cells, said BAPTA-AM increases the intracellular ATP level in LS8 cells, increases the mitochondrial DNA copy number in LS8 cells, increases the mitochondrial membrane potential in LS8 cells and decreases the level of mitochondrial fission protein Drp1 in LS8 cells.

Description

Application of BAPTA-AM in preparation of medicines for improving dental fluorosis Technical Field The invention belongs to the technical field of medicines, and particularly relates to an application of BAPTA-AM in preparation of a medicament for improving dental fluorosis. Background Fluorosis is a disease of ameloblastic dysfunction caused by excessive fluorine uptake during enamel development. The existing research shows that fluoride can interfere the energy metabolism of the mitochondria of the glazed cells, cause insufficient ATP synthesis, further destroy the calcium ion steady state in the cells, further aggravate the mitochondrial injury due to calcium overload caused by the blockage of calcium excretion, form vicious circle and finally cause abnormal enamel protein secretion and mineralization defect. The existing clinic lack of etiology treatment means with the aim of cytoprotection for the treatment of the dental fluorosis mainly dependent on aesthetic restoration after the tooth erupts, and the problems of long treatment period, high cost, no fundamentally preventing the development of the disease course and the like exist. BAPTA-AM is a precursor of a calcium chelator with cell membrane permeability, which is rapidly hydrolyzed to an active form in cells, efficiently and selectively buffers cytoplasmic calcium ions, and has long been used as a tool compound for studying calcium signaling. However, to date, no report has been made on the use of BAPTA-AM for the pharmaceutical use in the prevention and treatment of plaque and teeth or directly in the protection of the mitochondrial function of the enameloblasts. Disclosure of Invention Aiming at the defects of the prior art, the invention provides an application of BAPTA-AM in preparing medicines for improving the dental fluorosis, BAPTA-AM is used as an intracellular calcium ion chelating agent, and the damage of mitochondrial function is improved by reducing the concentration of free calcium ions in the glazed cells under the exposure of sodium fluoride, so that the normal mineralization of enamel is promoted, and a brand-new targeted intervention strategy is provided for the cellular mechanism of the dental fluorosis. In order to solve the technical problems, the technical scheme adopted by the invention is that the BAPTA-AM is applied to the preparation of the medicament for improving the dental fluorosis, and the BAPTA-AM has the structural formula: ; the BAPTA-AM is used for preparing medicines for improving the dental fluorosis. Preferably, the application comprises one or more of the following applications: The BAPTA-AM is used for improving the imbalance of the calcium ion homeostasis in LS8 cells induced by excessive sodium fluoride; the BAPTA-AM is used to ameliorate excessive sodium fluoride induced mitochondrial damage to LS8 cells. Preferably, when the BAPTA-AM is used to improve the excess sodium fluoride-induced imbalance in the steady state of calcium ions in LS8 cells, the BAPTA-AM is capable of reducing the concentration of calcium ions in LS8 cells and promoting calcium ion efflux. Preferably, when the BAPTA-AM is used to ameliorate excessive sodium fluoride-induced mitochondrial damage to LS8 cells, the BAPTA-AM can increase ATP levels within LS8 cells, increase LS8 cell mitochondrial DNA copy numbers, increase LS8 cell mitochondrial membrane potential, and decrease levels of mitochondrial mitotic protein Drp1 in LS8 cells. Compared with the prior art, the invention has the following advantages: the invention discloses BAPTA-AM for the first time, and the calcium steady state of the glazed cells is corrected, and the mitochondrial damage induced by fluorine is reversed, so that the development of the dental fluorosis is interfered at the aspect of etiology, and a brand new candidate substance and an explicit action target point are provided for the drug treatment of the dental fluorosis. The invention is described in further detail below with reference to the drawings and examples. Drawings FIG. 1 is a morphological diagram of LS8 cells after the action of different dose groups of NaF in example 1 of the present invention, wherein FIG. A is 0mmol NaF, FIG. B is 0.5mmol NaF, FIG. C is 1.0mmol NaF, and FIG. D is 1.5mmol NaF. FIG. 2 is a graph showing the effect of NaF on the intracellular and extracellular calcium ion concentrations of LS8 in example 1 of the present invention, wherein FIG. A is the fluorescence intensity of Fluo-4AM, FIG. B is the quantification of FIG. A, and FIG. C is the calcium ion concentration. FIG. 3 is a graph showing the change in intracellular ATP levels and mitochondrial DNA copy number of LS8 cells after NaF treatment in example 1 of the present invention, wherein graph A is the relative ATP levels and graph B is the relative mtDNA content. FIG. 4 is a graph showing changes in mitochondrial membrane potential of LS8 cells after treatment with NaF by JC-1 staining in example 1 of the present inven