Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Dexmedetomidine alleviates high glucose-induced podocyte damage by inhibiting EDA2R

Yongqiang Lin¹, Xiang Chen² , Zaizai Lin³, Weiwei Yan⁴

¹Department of Rehabilitation Medicine, Wenzhou Medical University, The First People’s Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province 317500, China; ²Department of Physical Medicine Rehabilitation, Wenzhou Medical University, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325027, China; ³Department of Rehabilitation Medicine, Wenzhou Medical University, The Health Education Center of Wenling, China; ⁴Department of Rehabilitation Medicine, The First People’s Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province 317500, China.

For correspondence:- Xiang Chen Email: x_chen0427@163.com Tel:+8657788002037

Accepted: 1 September 2022 Published: 30 September 2022

Citation: Lin Y, Chen X, Lin Z, Yan W. Dexmedetomidine alleviates high glucose-induced podocyte damage by inhibiting EDA2R. Trop J Pharm Res 2022; 21(9):1885-1891 doi: 10.4314/tjpr.v21i9.11

© 2022 The authors.
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Abstract

Purpose: To investigate the effect and mechanism of action of dexmedetomidine (Dex) on podocyte injury.

Methods: Cells were incubated with high glucose (50 mM) to induce a podocyte injury model in vitro. Cell viability, apoptosis, the expression of related protein related in podocyte injury and albumin permeability were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), flow cytometry, western blot and Transwell assays.

Results: Dex administration enhanced HG-induced cell viability and the relative protein expression of Bcl-2, but reduced the HG-induced relative protein level of Bax and apoptosisrate in podocytes (p < 0.05). Besides, Dex incubation compensated HG-induced relative protein expressions of nephrin and podocin in podocytes but did the reverse with regard to relative protein expression of desmin and albumin permeability (p < 0.05). Moreover, Dex treatment resulted in a decrease in ectodysplasin A2 receptor (EDA2R) expression in HG-induced podocytes. The level of EDA2R was upregulated by the transfection of overexpression plasmid containing the EDA2R sequences. Overexpression of EDA2R reversed Dex-induced increase in cell viability, apoptosis, expression of nephrin, podocin and desmin, as well as albumin permeability in HG-stimulated podocytes (p < 0.05).

Conclusion: Dex ameliorates HG-induced podocyte injury via inhibition of EDA2R, indicating that Dex is a potential alternative drug for the treatment of podocyte injury.

Keywords: Diabetic nephropathy, Dexmedetomidine, Podocyte, ectodysplasin A2 receptor (EDA2R)