AJP - GI Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 275: G1117-G1126, 1998;
0193-1857/98 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, J. H.
Right arrow Articles by Bouchier-Hayes, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J. H.
Right arrow Articles by Bouchier-Hayes, D.
Vol. 275, Issue 5, G1117-G1126, November 1998

Nitric oxide mediates hepatocyte injury

Jiang Huai Wang, H. Paul Redmond, Qiong Di Wu, and David Bouchier-Hayes

The Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin 9, Ireland

The degree of acute hepatic failure after severe trauma and sepsis is related to the extent of hepatocyte (HC) damage and cell death resulting from either necrosis or apoptosis. We have previously demonstrated that tumor necrosis factor-alpha (TNF-alpha ) and lipopolysaccharide (LPS) can directly lead to HC necrosis, but not apoptosis. To date, the reactive oxygen intermediates (ROI) and nitric oxide (NO) have been shown to play a potential role in the induction of cell apoptosis. However, it is unknown whether ROI and NO are involved in HC cell death. Therefore, in this study we tested the hypothesis that NO and ROI exert different effects on HC cell death. TNF-alpha and LPS alone failed to induce HC apoptosis but when combined with antioxidants resulted in HC apoptosis and DNA fragmentation, which is correlated with an increase in NO production. This effect was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Moreover, the NO donor sodium nitroprusside resulted in HC apoptosis and cell damage as represented by hepatocellular enzyme release. Antioxidants inhibited TNF-alpha - and LPS-mediated ROI generation and peroxynitrite formation in HC. TNF-alpha - and LPS-induced HC damage could be further reduced by the combination of antioxidants and L-NMMA. These results indicate that NO is involved in HC injury, primarily through the induction of HC apoptosis.

apoptosis; reactive oxygen intermediates; antioxidant; lipopolysaccharide; tumor necrosis factor-alpha ; peroxynitrite


This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. D. Halpern, H. Holubec, J. A. Dominguez, Y. G. Meza, C. S. Williams, M. C. Ruth, R. S. McCuskey, and B. Dvorak
Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis
Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G695 - G702.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
M. Pollack and C. Leeuwenburgh
Apoptosis and Aging: Role of the Mitochondria
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2001; 56(11): B475 - 482.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. P. Nadler, E. C. Dickinson, D. Beer-Stolz, S. M. Alber, S. C. Watkins, D. W. Pratt, and H. R. Ford
Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge
Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G173 - G181.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. Zhang, L. M. Walker, J. A. Hinson, and P. R. Mayeux
Oxidant Stress in Rat Liver after Lipopolysaccharide Administration: Effect of Inducible Nitric-Oxide Synthase Inhibition
J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 968 - 972.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. B. Mustafa and M. S. Olson
Effects of calcium channel antagonists on LPS-induced hepatic iNOS expression
Am J Physiol Gastrointest Liver Physiol, August 1, 1999; 277(2): G351 - G360.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online