PMID- 9142912
OWN - NLM
STAT- MEDLINE
DCOM- 19970606
LR  - 20181130
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 272
IP  - 4 Pt 1
DP  - 1997 Apr
TI  - TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in 
      cirrhotic rats.
PG  - G809-14
AB  - Cirrhotic rats exhibit increased susceptibility to ethanol-induced gastric 
      damage, but the underlying mechanism for this phenomenon remains unclear. 
      Abnormalities of the gastric microcirculation have been reported that may 
      contribute to the increased susceptibility to damage. Decreased gastric synthesis 
      of prostaglandins also likely contributes to impaired mucosal defense in 
      cirrhotic rats. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in 
      mucosal injury, and its synthesis can be inhibited by prostaglandins. Therefore, 
      we hypothesized that TNF-alpha synthesis/ release is altered in cirrhotic rats 
      and plays a role in the pathogenesis of ethanol-induced gastric damage. Cirrhosis 
      was induced by bile duct ligation, whereas controls had sham operations. Topical 
      application of 40% ethanol caused four times as much damage in cirrhotic rats 
      than in controls. Basal plasma TNF-alpha levels did not differ between control 
      and cirrhotic rats, although cirrhotic rats exhibited significantly higher levels 
      of gastric TNF-alpha mRNA. Plasma TNF-alpha increased significantly in control 
      and cirrhotic rats after ethanol administration. Inhibition of TNF-alpha 
      synthesis/release with pentoxifylline, thalidomide, dexamethasone, or 
      immunoneutralization of TNF-alpha (with anti-TNF-alpha) was found to 
      significantly reduce the severity of ethanol-induced gastric mucosal damage in 
      cirrhotic rats. We conclude that TNF-alpha contributes to the pathogenesis of 
      ethanol-induced gastric damage in cirrhotic rats.
FAU - Ferraz, J G
AU  - Ferraz JG
AD  - Intestinal Disease Research Unit, Faculty of Medicine, University of Calgary, 
      Alberta, Canada.
FAU - Tigley, A W
AU  - Tigley AW
FAU - Appleyard, C B
AU  - Appleyard CB
FAU - Wallace, J L
AU  - Wallace JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Immune Sera)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - *Ethanol/pharmacology
MH  - Gastric Mucosa/drug effects/metabolism
MH  - Immune Sera
MH  - Liver Cirrhosis, Experimental/*physiopathology
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stomach Diseases/*chemically induced
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/*physiology
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1152/ajpgi.1997.272.4.G809 [doi]
PST - ppublish
SO  - Am J Physiol. 1997 Apr;272(4 Pt 1):G809-14. doi: 10.1152/ajpgi.1997.272.4.G809.