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The effects of dantrolene and 2-aminoethoxydiphenyl borate (2-APB) on arsenic-induced osteoporosis

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Abstract

Background

Arsenic can increase the risk of osteoporosis among the population in arsenic–endemic areas compared with the general population in non-endemic areas. And calcium overload is the related mechanisms of arsenic-induced osteoporosis However, there is a relative lack of clinical research on the treatment of arsenic-induced osteoporosis. Dantrolene and 2-APB, as Ca2+ influx inhibitor, can reduce calcium overload and play an important role in the excitation–contraction coupling of skeletal muscle. Therefore, we study the effects of dantrolene and 2-APB on arsenic-induced osteoporosis in this study.

Objective

To study the effects of arsenic on the trabeculae of rats, and observe the effects of dantrolene and 2-aminoethoxydiphenyl borate (2-APB) on the trabeculae.

Results

Compared with the control group, some indices of micro-CT (BV/TV, Tb.Th, Tb.N, BMD, and DA) and the alkaline phosphatase (ALP) activity of bone marrow stromal cells (BMSCs) decreased, while some indices of micro-CT (Tb.Sp, Tb.Pf, and SMI), biochemical indicators (ALT, AST, ALP, and GGT), and the Ca2+concentration of BMSCs increased in the Sodium arsenite (NaAsO2) group (P < 0.05). Compared with the NaAsO2 group, the indices of micro-CT and biochemical indicators improved, the Ca2+ concentration of BMSCs decreased, and the ALP activity of BMSCs increased in the dantrolene group, 2-APB group and dantrolene + 2-APB group (P < 0.05), especially dantrolene + 2-APB group.

Conclusion

NaAsO2 can lead to osteoporosis in rats, dantrolene and 2-APB can reduce the degree of arsenic-induced osteoporosis.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (82160338), Youth Innovation and Talent Training Project of Shihezi University (CXPY202008), The School-level scientific research projects supported by Shihezi University (ZZZC202076 and ZZZC202196) and Key Research and Development Program of Sichuan Provincial Science and Technology Department (2022YFS0231).

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Author notes

  1. Wenjuan Qin, Jia Feng and Rongji Ma contributed equally to this work.

Authors and Affiliations

  1. Medical College of Shihezi University, Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China

    Wenjuan Qin & Jia Feng

  2. Medical College of Shihezi University, Department of Emergency, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China

    Rongji Ma

  3. School of Basic Medical Sciences, Chengdu Medical College, Chengdu, 610599, China

    Yufeng Jiang

  4. Chengdu Third People’s Hospital, Chengdu, 610031, China

    Hailong Lv

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  1. Wenjuan Qin
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Contributions

HLL and YFJ conceived and designed research. WJQ and JF conducted experiments. RJM analyzed data. WJQ, JF, and RJM wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Yufeng Jiang or Hailong Lv.

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Conflict of interest

Wenjuan Qin declares that she has no conflict of interest. Jia Feng declares that she has no conflict of interest. Rongji Ma declares that he has no conflict of interest. Yufeng Jiang declares that she has no conflict of interest. Hailong Lv declares that he has no conflict of interest.

Ethical approval

The experimental protocol has passed an ethical clearance of Medical Ethics Committee of the first affiliated Hospital of Medical College, Shihezi University and the approval number is A2020-167-01. All methods were carried out in accordance with the guidelines and regulations of experimental animals approved by the Medical Ethics Committee of the First Affiliated Hospital of Medical College, Shihezi University.

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Qin, W., Feng, J., Ma, R. et al. The effects of dantrolene and 2-aminoethoxydiphenyl borate (2-APB) on arsenic-induced osteoporosis. Mol. Cell. Toxicol. 19, 681–690 (2023). https://doi.org/10.1007/s13273-022-00294-2

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