N-acetylcysteine to ameliorate acute renal injury in a rat cardiopulmonary bypass model.

Abstract

OBJECTIVE: Oxidative stress and systemic inflammation response contribute to acute renal injury post cardiac surgery. We hypothesized that administration of the antioxidant N-acetylcysteine would be beneficial to renal function after cardiopulmonary bypass in a rat model. METHODS: Male Sprague-Dawley rats were divided into four groups (each n = 6): sham group, cardiopulmonary bypass group, and two N-acetylcysteine-treated cardiopulmonary bypass groups (bolus doses of 200 and 500 mg/kg in cardiopulmonary bypass prime). Blood samples were collected at the beginning of cardiopulmonary bypass, at the cessation of cardiopulmonary bypass, and at 2 and 12 postoperative hours. The kidneys were harvested at 12 postoperative hours. RESULTS: Serum creatinine and cystatin C continuously increased in all cardiopulmonary bypass groups (P < .05 within groups). Tubular dilatation, tubular necrosis, and vacuole formation were found in epithelial cells in histomorphologic studies of the cardiopulmonary bypass groups, but N-acetylcysteine significantly reversed these effects (P < .05 between groups). Compared with the sham group, the reduced glutathione hormone content and the superoxide dismutase and catalase activities decreased in the cardiopulmonary bypass groups (P < .01). N-acetylcysteine-treated groups had higher levels of these antioxidants than the untreated bypass group (P < .05). Renal malondialdehyde, tumor necrosis factor alpha, and nuclear factor kappaB were notably increased in all cardiopulmonary bypass groups relative to the sham group (P < .01), and N-acetylcysteine attenuated these changes dose dependently. CONCLUSION: Administration of the antioxidant N-acetylcysteine preserved renal function after cardiopulmonary bypass dose dependently. Furthermore, oxidative stress and systemic inflammation were significantly reduced in the treated animals.