Attenuation of renal ischemia–reperfusion injury by postconditioning involves adenosine receptor and protein kinase C activation

Abstract

Summary Significant organ injury occurs after transplantation and reflow (i.e., reperfusion injury). Postconditioning (PoC), consisting of alternating periods of reperfusion and re‐occlusion at onset of reperfusion, attenuates reperfusion injury in organs including heart and brain. We tested whether PoC attenuates renal ischemia–reperfusion (I/R) injury in the kidney by activating adenosine receptors (AR) and protein kinase C (PKC). The single kidney rat I/R model was used. Groups: (1) sham: time‐matched surgical protocol only. In all others, the left renal artery (RA) was occluded for 45 min and reperfused for 24 h. (2) Control: I/R with no intervention at R. All antagonists were administered 5 min before reperfusion. (3) PoC: I/R + four cycles of 45 s of R and 45 s of re‐occlusion before full R. (4) PoC + ARi: PoC plus the AR antagonist 8‐ρ‐(sulfophenyl) theophylline (8‐SPT). (5) PoC + PKCi: PoC plus the PKC antagonist chelerythrine (Che). In shams, plasma blood urea nitrogen (BUN mg/dl) at 24 h averaged 23.2 ± 5.3 and creatinine (Cr mg/dl) averaged 1.28 ± 0.2. PoC reduced BUN (87.2 ± 10 in Control vs. 38.8 ± 9, P = 0.001) and Cr (4.2 ± 0.6 in Control vs. 1.5 ± 0.2, P < 0.001). 8‐SPT and Che reversed renal protection indices after PoC. I/R increased apoptosis, which was reduced by PoC, which was reversed by 8‐SPT and Che. Postconditioning attenuates renal I/R injury by adenosine receptor activation and PKC signaling.

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

“…23 ROS activate a host of pathological processes including DNA damage, protein oxidation and nitrosylation, lipid peroxidation, and induction of apoptosis. 24 Indeed, peroxidation of membrane lipids can disrupt membrane fluidity and cell compartmentalization, which can result in cell lysis.…”

Treatment with a Novel Hypoxia-Inducible Factor Hydroxylase Inhibitor (TRC160334) Ameliorates Ischemic Acute Kidney Injury

“…More delayed ischemic postconditioning, starting 6 and 24 h after focal and global cerebral ischemia, respectively, has also been described [12]. Studies with ischemic postconditioning (brief interruption of blood flow) leading to amelioration of renal injury have also been reported in animal models of I/R induced AKI [13,14,15,16,17,18]. In most of these studies HIF activation is one of the predominant mechanisms implicated for the observed tissue salvaging effects of postconditioning.…”

Inhibiting inducible nitric oxide synthase with rutin reduces renal ischemia/reperfusion injury

“…1 Many scientists report that renal I/R injury is a common cause of renal cell death, acute renal failure and, in the case of transplantation, delayed graft function or graft rejection. [2][3][4] Many mediators are involved in the pathophysiology of I/R injury, including reactive oxygen species (ROS), reactive nitrogen species (RNS), purine metabolites, neutrophil accumulation, vasoactive substance (endothelin, angiotensin II) and subsequent release of lytic enzymes.…”