Protective effects of melatonin and N-acetylcysteine on hepatic injury in a rat cardiopulmonary bypass model.
BACKGROUND
An increasing number of patients were undergoing cardiac surgery with cardiopulmonary bypass (CPB) and more attention had been paid to hepatic injury after CPB. This study was designed to test the hypothesis that melatonin and N-acetylcysteine (NAC) could attenuate hepatic injury induced by CPB in rats.


METHODS
Male Sprague Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), NAC (CPB + 250 mg/kg N-acetylcysteine), and melatonin (CPB + 20 mg/kg melatonin). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2, 3, and 24 h postoperation. Liver samples were harvested at 24 h after the operation.


RESULTS
In the control group, the levels of serum liver enzymes and tumor necrosis factor-alpha, activities of inducible nitric oxide synthase, malondialdehyde, and myeloperoxidase in liver tissue were significantly increased. In addition, swollen hepatocytes, vacuolization, and congestion in sinusoids were observed. These changes were markedly reversed in both NAC and melatonin groups. Furthermore, the glutathione content and liver antioxidative enzymes activities were significantly decreased in the control group compared with the sham group. However, the levels of these antioxidants were markedly elevated after NAC or melatonin treatment compared with placebo treatment.


CONCLUSIONS
Our findings showed that NAC and melatonin had acceptably beneficial effects against the CPB-induced hepatic injury.
Huang
Hairong
H
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.
Yin
Rong
R
Zhu
Jiaquan
J
Feng
Xiaomei
X
Wang
Changtian
C
Sheng
Yi
Y
Dong
Guohua
G
Li
Demin
D
Jing
Hua
H
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D005978:Glutathione; D008550:Melatonin; D000111:Acetylcysteine