Exogenous melatonin ameliorates hepatic injury in a rat cardiopulmonary bypass model.
Hepatic injury after cardiac surgery was considered to be a consequence of cardiopulmonary bypass (CPB). This study tested the hypothesis that melatonin could attenuate the hepatic injury in a rat CPB model. Male Sprague-Dawley rats were randomly divided into four groups: sham-operation group, control group (given an equal volume of vehicle), low dose melatonin (10 mg/kg) treated group and high dose melatonin (20 mg/kg) treated group. Blood samples were collected at the beginning, at the cessation of CPB, and at 30 min, 1, 2, 3 and 24 h post-operation. Liver samples were harvested at 24 h after operation. The serum indices of the liver enzymes and systemic inflammation, as well as oxidative stress indices and the Ca++-ATPase activity of liver tissues were determined. In the control animals, the indices of liver enzymes, tumor necrosis factor-alpha (TNF-alpha) increased after operation, and liver inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), myeloperoxidase (MPO) increased as well. However, the activities of liver antioxidative enzymes and the concentration of glutathione (GSH) decreased remarkably. Results in melatonin group showed that melatonin reversed all the biochemical changes, but there was no significant difference between the melatonin-treated groups. In addition, histological findings further supported these results. All results indicated that application of exogenous melatonin during operation preserves liver function by reducing oxidative stress and the systemic inflammatory response.
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, 305 East Zhongshan Road, Nanjing 210002, China.
Hairong
H
Huang
Rong
R
Yin
Jiaquan
J
Zhu
Xiaomei
X
Feng
Changtian
C
Wang
Yi
Y
Sheng
Guohua
G
Dong
Demin
D
Li
Hua
H
Jing
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D008315:Malondialdehyde; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D005978:Glutathione; D008550:Melatonin; D010100:Oxygen