Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2005; 11(13): 1951-1956
Published online Apr 7, 2005. doi: 10.3748/wjg.v11.i13.1951
Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats
Mukaddes Esrefoglu, Mehmet Gül, Memet Hanifi Emre, Alaattin Polat, Mukadder Ayse Selimoglu
Mukaddes Esrefoglu, Mehmet Gül, Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey
Memet Hanifi Emre, Alaattin Polat, Department of Physiology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey
Mukadder Ayse Selimoglu, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Mukaddes Esrefoglu, inonu Universitesi, Tlp Fakültesi, Histoloji ve Embriyoloji Anabilim Dall, 44128 Malatya, Turkey. drmukaddes@hotmail.com
Telephone: +90-422-3410660 Fax: +90-422-3410036
Received: October 23, 2004
Revised: October 24, 2004
Accepted: November 29, 2004
Published online: April 7, 2005
Abstract

AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury.

METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 µg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOX) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system.

RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOX, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOX levels of SO group were 147.47±6.69, 0.88±0.33 µmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 µmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8, 0.74±0.02 µmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOX levels.

CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.

Keywords: Cholestasis; Melatonin; Oxidative stress; Free radicals; Hepatic injury