The effects of TRPM2, TRPM6, TRPM7 and TRPM8 gene expression in hepatic ischemia reperfusion injury.

Abstract

Mammalian transient receptor potential melastatin (TRPM) channels are a form of calcium channels and they transport calcium and magnesium ions. TRPM has eight subclasses including TRPM1-8. TRPM2, TRPM6, TRPM7, TRPM8 are expressed especially in the liver cell. Therefore, we aim to investigate the effects of TRPM2, TRPM6, TRPM7, and TRPM8 gene expression and histopathologic changes after treatment of verapamil in the hepatic ischemia-reperfusion rat model. Animals were randomly assigned to one or the other of the following groups including sham (n=8) group, verapamil (calcium entry blocker) (n=8) group, I/R group (n=8) and I/R- verapamil (n=8) group. TRPM 2, 6, 7, 8 gene expression level was were assessed by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and histopathologic changes were determined by the hematoxylin and eosin (HE) examination. The expression level of TRPM 2, 6, 7, and 8 genes was were significantly higher in ischemia-reperfusion (I/R), verapamil, IR-verapamil groups compared to sham group. The p-values were 0.0024, < 0.0001, 0.0002, 0.006 for TRPM2, TRPM6, TRPM7, and TRPM8, respectively. Severe necrotic, degenerative differentiations and severe hemorrhagic areas were observed in hepatocytes from IR group. Also, moderate necrotic and degenerative differentiations and moderate hemorrhagic areas were observed in hepatocytes from IR-verapamil group. This is the first study reporting an association between the expression level of TRPM 2, 6, 7, 8 in a hepatic ischemia-reperfusion rat model. Moreover, TRPM 2, 6, 7, 8 affect hepatic ischemia-reperfusion.