Curcumin Modulates Renal Ischemia Reperfusion Injury via Down Regulation of AKT mTOR Pathway

Abstract

Aim: The study aimed to investigate the potential protective effect of curcumin on renal IRI in rats model by regulation of Akt/mTOR pathway.
Materials and Methods: In this study, adult male rats with 15-28 weeks in age and 300-350 g in weight divided randomly into 4 equal groups (6 rats in each group): sham group, control group, vehicle group and curcumin treated group. Rats were exposed to bilateral renal ischemia for 30 min by renal pedicles clamping and 2 hr reperfusion. Curcumin was administrated intraperitoneally at dose of 60 mg/kg 45 min before ischemia. At the end of reperfusion, collection of blood and renal tissue samples was performed for measurement of the following parameters: Interleukin-1β (IL-1β), caspase-3, F2-isoprostane, mTOR, p-mTOR, Akt and p-Akt estimated in homogenization of frozen renal tissues by using ELISA. Serum urea and creatinine by using colorimetric method. Histopathological analysis.
Results: At the end of experiment, the serum levels of urea and creatinine and renal levels regarding p-mTOR, p-Akt, IL-1β, caspase-3, and F2-isoprostane are recognized to be significantly (p<0.05) elevated in control group when compared with sham group. Histopathological analysis of the renal tissues recognizes a severe renal injury in control group and there is a significant role of curcumin in ameliorating this injury by minimizing the serum level of urea and creatinine, tissue level of IL-1β, caspase-3, F2-isoprostane except for p-mTOR and p-AKt levels which were significantly (p<0.05) higher in comparison with that of control group.
Conclusion: From the overall results, curcumin significantly diminishes renal ischemia reperfusion injury in the rat model through Akt/mTOR pathway by its effect as anti-oxidant, anti-inflammatory and anti-apoptotic.