Mitigative Role of Cysteamine Against Unilateral Renal Artery Occlusion-induced Reperfusion Injury via Inhibition of Aopp, p65nfkb, and Pro-apoptotic Caspase 3

Abstract

Abstract Purpose Ischemia-reperfusion injury (IRI) is unavoidable during kidney transplant and it is responsible for delayed or non-function after kidney transplantation. Cysteamine has been reported to possess activity against pathways of reperfusion injury. Thus, we designed this study to investigate its potential against renal reperfusion injury.Methods Twenty-eight male Wistar rats were divided into four groups (seven rats per group): sham, IRI, IRI plus 50 mg/kg cysteamine treatment, and IRI with 50 mg/kg cysteamine treatment. The right renal artery was clamped without crushing to induce ischemia for 45 minutes and later sutured. After 30 minutes, the clamp was removed to induce reperfusion injury for 24 hours. Activities of protein thiol, H2O2, GPx, GSH, and MDA were estimated. The serum level of creatinine, AOPP, nitrite, MPO, TNF-α, and IL-1β was evaluated. The expression of p65NFkB and caspase 3 were assessed by immunohistological technique. The p < 0.05 indicate a significant resultResults Significant elevation of H2O2, MDA, and nitrite and reduced GPx, GSH, and protein thiol in the IRI rats was reversed by cysteamine (50 and 100 mg/kg). Serum MPO, TNF-α, IL-1β, creatinine, and AOPP were significantly elevated in IRI while rats treated with cysteamine revealed a significant decrease (p < 0.05) in the activities of these pro-inflammatory and renal injury markers.Conclusion Based on its activity against inflammation, apoptosis, and free radical-induced stress, cysteamine has great potential of being used as a kidney transplant pre-operative drug to prevent renal reperfusion injury.