8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury

  • J Cell Physiol. 2019 Apr;234(4):4572-4581. doi: 10.1002/jcp.27236.
Ersen Eraslan  1 ,  Ayhan Tanyeli  2 ,  Elif Polat  3 ,  Elif Polat  4
Affiliations
  • 1. Department of Physiology, Faculty of Medicine, University of Bozok, Yozgat, Turkey.
  • 2. Department of Physiology, Faculty of Medicine, University of Atatürk, Erzurum, Turkey.
  • 3. Department of Biochemistry, Faculty of Medicine, University of Atatürk, Erzurum, Turkey.
  • 4. Department of Histology and Embryology, Faculty of Medicine, University of Namık Kemal, Tekirdağ, Turkey.
PMID: 30191993 DOI: 10.1002/jcp.27236
Abstract

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na+ and CA 2+ . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, Renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of Caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.

Keywords
8-Br-cADPR; TRPM2; cytokines; ischemia-reperfusion; oxidative stress.
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