Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats
Küçük Resim Yok
Tarih
2005
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Baishideng Publ Grp Co Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 mu g/(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 (NO(X)) 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 NO(X), and a significant decrease in GSH levels. Mean +/- SE values of MDA, GSH and NO(X) levels of SO group were 147.47 +/- 6.69, 0.88 +/- 0.33 mu mol/g and 180.70 +/- 6.58 nm/g, respectively. The values of BDL group were 200.14 +/- 21.30, 0.65 +/- 0.02 mu mol/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 mu mol/g, and 290.38 +/- 32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NO(X) 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. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.
Açıklama
Anahtar Kelimeler
Cholestasis, Melatonin, Oxidative stress, Free radicals, Hepatic injury
Kaynak
World Journal of Gastroenterology
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
11
Sayı
13
