Effect of Thymoquinon on TRPM Channels in Rats with Liver Ischemia

Abstract

Abstract Ischemia/Reperfusion (I/R) injury is surgery and clinically important problem. It was showed that Ca+ 2 concentration increases into cell with I/R injury. TRPM channels have a role in determining the amount of Ca+ 2 concentration into cell. Thymoquinone (Tmq) which was isolated from Nigella Sativa, particularly has the beneficial effects such as antioxidant, anticancerogenic, antiinflamatuar. We aimed to investigate the antioxidant and histopathologic effect of thymoquinone in hepatic I/R rat model. In addition the other purpose of the our study was determination effects of thymoquinone on levels of TRPM gene expression. Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Shame; Group 3: Hepatic I/R (45min/45min); Group 4: Tmq (50 mg/kg); Group 5: Tmq + I/R (ten days before from I/R at dose 50 mg/kg of Tmq by oral gavage.) Hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular a clamp in ischemia groups. The liver tissues and blood samples which were taken at the end of study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL and apoptosis parameters statistically decreased in Tmq and Tmq + I/R groups in comparision with I/R group in histopathological evaluation. It was obsorved that biochemical parameters, AST, ALT, GGT, LDH, creatinine and urea levels significantly increased in I/R group as compared with, shame, Tmq and Tmq + I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq + I/R groups as compared to I/R group. Based on our findings it was observed that application of Tmq in the treatment of liver diseases associated with I/R injury is important in terms of both ischemia and apoptosis and also using in the treatment of liver-related diseases. Additionally we showed that thymoquinone may inhibit Ca+ 2 entry into the cell by reducing TRPM2,6,7,8 gene expression. In conclusion this situation is brought to mind that cell injury related with I/R is reduced by Tmq.