Evaluation the Nephroprotective Effect of Rosuvastatin through Activation of NrF2\HO1 Pathway in Renal Ischemia Reperfusion Injury in Rats

Abstract

Background: When ischemic tissues are rapidly reperfused by blood, the endothelial layer of capillaries creates reactive oxygen species (ROS), which worsens the NFκB pathway and inflammatory process. Ischemia also causes structural and functional alterations in the microvascular system.  Numerous components of inflammation are produced, including NFκB, IL-1β, and KIM1.  The main cause of morbidity and mortality in some disorders, such as sepsis, MI, and AKI, seems to be ischemia reperfusion damage.

Objective: This study is occurred to check the effectiveness of Rosuvastatin in attenuating renal injury during IR, possibly through activation of Nrf2\HO1 signaling pathway.

Method: Twenty Wister Albino rats were divided into four equal groups at random, (N=5): Sham: Rat laparotomies were performed without ischemia. Control: Rats undergone laparotomy with bilateral RIRI for 30-minute following two hours of reperfusion. Vehicle: Rats given an intraperitoneal injection of DMSO three days before induction of RIRI. Rosuvastatin: Rats received an intraperitoneal injection of Rosuvastatin three days prior to RIRI.

Results: NFκB, IL-1β, and KIM-1 tissue levels were significantly lower in the sham than in the vehicle and control; the results also revealed that Rosuvastatin had significantly lower levels of KIM-1, NFκB, IL-1β than in the vehicle and control; and the histopathology demonstrated that Rosuvastatin could significantly reduce kidney damage compared to the vehicle and control. On the other hand, tissue content of Nrf2\HO1 was elevated in Rosuvastatin group compared to I\R group.

Conclusion: This study concluded that Rosuvastatin significantly reduced RIRI damage in rats through activation of Nrf2\HO1 antioxidant signaling pathway.