Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps://ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Nov;32(5):1008-17.
doi: 10.1053/jhep.2000.19621.

Exacerbation of alcoholic liver injury by enteral endotoxin in rats

P Mathurin1, Q G Deng, A Keshavarzian, S Choudhary, E W Holmes, H Tsukamoto
Affiliations

Exacerbation of alcoholic liver injury by enteral endotoxin in rats

P Mathurinet al. Hepatology. 2000 Nov.

Abstract

肠道通透性增加(肠漏)和内毒素in-mediated Kupffer cell activation are proposed as the mechanisms of alcoholic liver injury. Although ethanol feeding is shown to sensitize the liver for injury induced by parental administration of lipopolysaccharide (LPS), how enteral LPS loading affects alcoholic liver injury is yet to be tested. The present study provides direct evidence for enhanced entrance to portal circulation of LPS enterally administered to the intragastric ethanol infusion model. Portal and systemic blood endotoxin levels increased to 43.0 +/- 4.1 and 6.2 +/- 4.3 pg/mL at 2 hours following enteral LPS administration (5 mg/kg) in alcohol-fed animals, while no such increases were observed in pair-fed controls. However, endotoxin levels in systemic blood of alcohol-fed rats were reduced to 0 to 1. 5 pg/mL 16 hours after LPS administration. Weekly enteral administration of LPS to the model for 9 weeks exacerbated an increase in plasma alanine transaminase (ALT) levels (227 +/- 75 vs. 140 +/- 70; P <.01), mononuclear infiltration (25 +/- 22 vs. 6.4 +/- 4.4/10 mm(2); P =.02), sinusoidal congestion, and spotty necrosis, and induced diffuse coagulative necrosis and centrilobular fibrosis in some animals. Reverse-transcription polymerase chain reaction (RT-PCR) analysis confirmed the LPS effect at the tissue level by demonstrating accentuated induction of tumor necrosis factor alpha (TNF-alpha) and Cox-2 mRNA. In conclusion, enteral LPS administration potentiates alcoholic liver necrosis, inflammation, and fibrosis despite efficient endotoxin clearance by the liver and mild systemic endotoxemia that occurs episodically following enteral LPS challenge.

Similar articles

看到所有类似的文章

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources