N-acetyl cysteine amide mitigates oxidative stress and apoptosis in a rat model of renal ischemia-reperfusion injury.

Renal ischemia–reperfusion (IR) injury is a major cause of acute kidney injury, in which oxidative stress (OS) and apoptosis play central roles. N-acetyl cysteine amide (NACA), a lipophilic derivative of N-acetylcysteine, exhibits improved cellular penetration and antioxidant activity. This study investigated the renoprotective effects of NACA in a rat model of renal IR injury. Twenty-eight female Wistar albino rats were randomized into four groups (n = 7): Control, IR, NACA + IR (100 mg/kg i.p., 30 min before ischemia), and IR + NACA (100 mg/kg i.p., immediately after ischemia). Following right nephrectomy, the left renal pedicle was clamped for 60 min and reperfused for 24 h. Serum renal function markers, kidney OS parameters, histopathological injury, and caspase-3 immunoreactivity were evaluated. Renal IR injury significantly increased serum blood urea nitrogen and creatinine levels and induced histopathological damage characterized by tubular dilatation, cast formation, and degeneration. Catalase (CAT) and superoxide dismutase (SOD) activities were significantly altered; malondialdehyde increased after IR and was reduced by NACA pretreatment, whereas myeloperoxidase and total glutathione did not differ significantly among groups. NACA pretreatment attenuated inflammatory cell infiltration, tubular dilatation, and caspase-3 immunoreactivity, while partially restoring CAT and SOD activity. Post-ischemic NACA administration was less effective, particularly in reducing apoptosis and inflammatory infiltration. NACA confers partial renoprotection against renal IR injury, with pretreatment providing superior efficacy. These findings highlight the importance of antioxidant timing and suggest NACA as a potential prophylactic strategy when renal ischemia is predictable.