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Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway

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Abstract

Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.

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Acknowledgments

The authors thank Dr. Mohammad Jafari, pharmacologist, for her helpful assistance in designing the study and analyzing collected data.

Author information

Author notes

  1. Mohsen Chamanara and Ahmad Reza Dehpour contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran

    Mostafa Akbariani & Ehsan Nasiroleslami

  2. Toxicology Research Center, AJA University of Medical Sciences, Tehran, Iran

    Mostafa Akbariani, Zahra Hami, Ehsan Nasiroleslami & Mohsen Chamanara

  3. Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farahnaz Bidari Zerehpoosh

  4. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Zohreh Shahabi

  5. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Amir Shadboorestan

  6. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran

    Sevda Shayesteh

  7. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Reza Dehpour

  8. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Ahmad Reza Dehpour

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  1. Mostafa Akbariani
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Contributions

Conceptualization: ARD, MCh and MA; Methodology: ARD; Validation: MCh, ZH and EN; Formal analysis: ASh and SSh; investigation: MA and FBZ; Writing, original draft preparation: MA, ZSh; Writing, review and editing: Ash, MCh and ARD; Supervision: MCh and ARD. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Mohsen Chamanara or Ahmad Reza Dehpour.

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The protocols for this study received approval from the ethics committee of the School of Medicine at Aja University of Medical Sciences (project code of ethics: IR.AJAUMS.REC.1401.079).

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The authors declare no competing interests.

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Akbariani, M., Bidari Zerehpoosh, F., Shahabi, Z. et al. Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-023-02922-7

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