PMID- 15309720
OWN - NLM
STAT- MEDLINE
DCOM- 20041216
LR  - 20190430
IS  - 1007-9327 (Print)
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Linking)
VI  - 10
IP  - 18
DP  - 2004 Sep 15
TI  - Protective effect of melatonin against liver injury in mice induced by Bacillus 
      Calmette-Guerin plus lipopolysaccharide.
PG  - 2690-6
AB  - 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.
FAU - Wang, Hua
AU  - Wang H
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, Anhui 
      Province, China.
FAU - Wei, Wei
AU  - Wei W
FAU - Shen, Yu-Xian
AU  - Shen YX
FAU - Dong, Chen
AU  - Dong C
FAU - Zhang, Ling-Ling
AU  - Zhang LL
FAU - Wang, Ni-Ping
AU  - Wang NP
FAU - Yue, Li
AU  - Yue L
FAU - Xu, Shu-Yun
AU  - Xu SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Cells, Cultured
MH  - Free Radical Scavengers/*pharmacology
MH  - Hepatocytes/cytology/drug effects/metabolism
MH  - Interleukin-1/metabolism
MH  - Kupffer Cells/cytology/drug effects/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Liver Diseases/*drug therapy/immunology/metabolism
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Melatonin/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Mycobacterium bovis
MH  - Nitric Oxide/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Superoxide Dismutase/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4572194
EDAT- 2004/08/17 10:00
MHDA- 2004/12/17 09:00
PMCR- 2004/09/15
CRDT- 2004/08/17 10:00
PHST- 2004/08/17 10:00 [pubmed]
PHST- 2004/12/17 09:00 [medline]
PHST- 2004/08/17 10:00 [entrez]
PHST- 2004/09/15 00:00 [pmc-release]
AID - 10.3748/wjg.v10.i18.2690 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2004 Sep 15;10(18):2690-6. doi: 10.3748/wjg.v10.i18.2690.