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


CONCLUSIONS
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.
Zhu
Jiaquan
J
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China. doctor_zhujq@yahoo.com.cn
Yin
Rong
R
Shao
Hongtao
H
Dong
Guohua
G
Luo
Liguo
L
Jing
Hua
H
D000111:Acetylcysteine / Q000008:administration & dosage*; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000032:analysis; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011183:Postoperative Complications / Q000188:drug therapy; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012680:Sensitivity and Specificity
D018836:Inflammation Mediators; D000111:Acetylcysteine