Effects of propofol preconditioning and mechanical ischemic preconditioning on renal ischemia-reperfusion injury and the role of pyroptosis

Renal ischemia-reperfusion (IR) injury occurs as a consequence of arterial occlusion, shock, and organ transplantation, leading to significant problems such as acute kidney injury, delayed graft function, and renal graft rejection. Strategies to prevent delayed graft function have thus gained importance in transplantation. Hence, augmenting organs' ability to withstand ischemic injury is crucial. Ischemic postconditioning (PostC) is based on the concept of inducing endogenous protective mechanisms by applying short cycles of ischemia during reperfusion following prolonged ischemic periods. In this study, we aimed to investigate the role of inflammatory signaling molecules and pyroptosis, the form of cell death associated with inflammation, in IR injury. Furthermore, we compared the effects of mechanical ischemic postconditioning and propofol postconditioning on this inflammatory cell death pathway. A total of 40 male Sprague-Dawley rats weighing 250-280 g were randomized into 5 groups. After performing a right nephrectomy, left renal artery occlusion was performed and was followed by 60 minutes of ischemia and 24 hours of reperfusion. PostC was applied as 6 cycles of 10 seconds reperfusion/10 seconds ischemia at the onset of reperfusion. Propofol at a dose of 25 mg/kg was intraperitoneally administered immediately before reperfusion. Inflammatory signaling molecules (NF-κB, TNF-α, IL1-β, IL-6, IL-10) and the pyroptosis indicator, gasdermin, were analyzed using Western blot. Histopathological alterations were also assessed. Levels of inflammatory molecules (NF-κB, TNF-α, IL1-β, IL-6, IL-10) significantly escalated with IR. However, PostC and propofol interventions significantly decreased this escalation. The pyroptosis indicator, gasdermin levels exhibited a marked increase in IR compared to the control group, which was attenuated by PostC and propofol treatments. Histopathological changes (tubular necrosis, tubular protein content, edema, hemorrhage, inflammation, glomerular shrinkage, glomerular fluid retention) augmented with IR but were decreased with the intervention measures. These findings underscore the role of the inflammatory pathway and pyroptosis in IR injury and suggest that mechanical ischemic postconditioning and propofol pharmacological postconditioning may offer protective effects by modulating these pathways. In scenarios involving IR injury such as arterial occlusion, shock, and organ transplantation, ischemic postconditioning and propofol may reduce inflammation and pyroptosis, potentially averting acute kidney injury, delayed graft function, and renal graft rejection. The anesthetic propofol, with therapeutic effects similar to mechanical ischemic postconditioning (even more protective), could potentially serve as a suitable pharmacological preconditioning agent, and its application as an anesthetic in situations involving IR injury, such as organ transplantation, may be considered."