当前位置： SCI文献检索 > WORLD JOURNAL OF GASTROENTEROLOGY期刊下所有文献 > Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide.

Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide.

Abstract：

AIM:To investigate the effects and mechanisms of melatonin on immunological liver injury in mice. METHODS:A model of liver injury was induced by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice. Kupffer cells and hepatocytes were isolated and cultured according to a modified two-step collagenase perfusion technique. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO), content of malondiadehyde (MDA), activity of superoxide dismutase (SOD), were measured by biochemical methods. Tumor necrosis factor-alpha (TNF-alpha) activity was determined by RIA. Interleukin (IL)-1 activity was measured by thymocyte proliferation bioassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS:Immunological liver injury induced by BCG+LPS was successfully duplicated. Serum transaminase (ALT, AST) activities were significantly decreased by melatonin (0.25, 1.0, 4.0 mg/kg bm). Meanwhile, MDA content was decreased and SOD in liver homogenates was upregulated. Furthermore, pro-inflammatory mediators (TNF-alpha, IL-1, NO) in serum and liver homogenates were significantly reduced by melatonin. Histological examination demonstrated that melatonin could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. In in vitro experiment, TNF-alpha was inhibited at the concentrations of 10(-8)-10(-6) mol/L of melatonin, while IL-1 production of Kupffer cells induced by LPS (5 microg/mL) was decreased only at the concentration of 10(-6) mol/L of melatonin, but no effect on NO production was observed. Immunological liver injury model in vitro was established by incubating hepatocytes with BCG- and LPS-induced Kupffer cells. Activities of ALT, TNF-alpha, IL-1, and MDA in supernatant were significantly increased. Melatonin had little effect on the level of ALT, but reduced the content of TNF-alpha and MDA at concentrations of 10(-7)-10(-5) mol/L and decreased the content of IL-1 at concentrations of 10(-6)-10(-5) mol/L. CONCLUSION:Melatonin could significantly protect liver injury in mice, which was related to free radical scavenging, increased SOD activity and pro-inflammatory mediators.

journal_name

World J Gastroenterol

journal_title

World journal of gastroenterology

authors

Wang H,Wei W,Shen YX,Dong C,Zhang LL,Wang NP,Yue L,Xu SY

doi

10.3748/wjg.v10.i18.2690

keywords:

subject

Has Abstract

pub_date

2004-09-15 00:00:00

pages

2690-6

issue

eissn

1007-9327

issn

2219-2840

journal_volume

pub_type

杂志文章

在线工具

Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide.