Involvement of necroptosıs and apoptosıs ın protectıve effects of cyclosporın a on ischemıa-reperfusıon injury in rat kıdney

Abstract

We aimed to investigate the protective effects of low dose cyclosporin A (CsA) on ischemia–reperfusion (IR) injury in rat the kidney and on the apoptotic and necroptotic mechanisms involved. 1. Control group (received a single intraperitoneal (i.p.) dose of 1 ml sterile saline 15 min before the surgical procedure), 2. IR group (was subjected to 30 min of bilateral kidney ischemia followed by 90 min of reperfusion; and received a single i.p. dose of 1 ml sterile saline 15 min before the IR procedure, 3. IR + CsA group (received a single i.p. dose of 3 mg/kg CsA 15 min before the IR procedure. Renal functions (renal perfusion pressures, and serum urea-creatinine levels), kidney histological scores, MDA levels, and TNF-α, caspase-3, RIP1, RIP3, MLKL, CaMKII and CypD protein expressions were also measured. Renal perfusion pressures (PP), serum urea and creatinine levels, renal tissue MDA levels, and the protein expression levels of TNF-α, caspase-3, RIP1, RIP3, MLKL, CAMKII and CypD were significantly increased in the IR group compared to the control group (p < 0.05), Additionally, there were significant decreases in all the parameters in the IR + CsA group compared to those in the IR group (p < 0.05). Furthermore, histopathological analyses revealed significantly higher kidney injury scores in the IR group compared to the control group, and low dose CsA treatment improved the injury. A single low dose of CsA injection 15 min before IR, demonstrated a protective effect on bilateral renal IR injury and a reduction in apoptotic and necroptopic markers which is resulted in improvement of renal functions.