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

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. In the current manuscript, using immunohistochemical and biochemical approaches we have, for the first time, presented evidence indicating that transient receptor potential melastatin‐2 ion channel prevent renal ischemia–reperfusion injury.