Evidence map›Paper›PMID 25462064›Full record

ReviewRedox biology2014

Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness.

Christopher B Forsyth, Robin M Voigt, Ali Keshavarzian

Open access · goldAbstract readReview
In one paragraph

Review in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 2 countries.

Christopher B ForsythDepartment of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA; Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA. Electronic address: christopher_b_forsyth@rush.edu.
Robin M VoigtDepartment of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA.
Ali KeshavarzianDepartment of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA; Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA; Department of Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, IL, USA; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Rush University Medical Center · US

Funding

Alcohol, iNOS upregulation, leaky gut &liver diseaseR01AA013745 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI KESHAVARZIAN, ALI · 2003 to 2009
$3.3M
Brain-gut circadian rhythm interactions in alcohol-induced gut leakinessR01AA020216 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI KESHAVARZIAN, ALI, TUREK, FRED W · 2010 to 2014
$3.0M
Role of Alcohol and Circadian Disruption in Inflammation and Colon CancerR01AA023417 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI KESHAVARZIAN, ALI, KHAZAIE, KHASHAYARSHA · 2014 to 2018
$2.0M
Systems Biology Approach to Identifying Biomarkers for Alcoholic Liver DiseaseRC2AA019405 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI GILLEVET, PATRICK MARTIN, KESHAVARZIAN, ALI · 2009 to 2010
$2.0M
NIAAA NIH HHS AA013745NIAAA NIH HHS AA020216NIAAA NIH HHS AA023417NIAAA NIH HHS R01 AA013745NIAAA NIH HHS R01 AA020216NIAAA NIH HHS R01 AA023417NIAAA NIH HHS RC2 AA019405NIAAA NIH HHS RC2AA019405
6 · The paper itself

Abstract

Chronic alcohol use can result in many pathological effects including alcoholic liver disease (ALD). While alcohol is necessary for the development of ALD, only 20-30% of alcoholics develop alcoholic steatohepatitis (ASH) with progressive liver disease leading to cirrhosis and liver failure (ALD). This suggests that while chronic alcohol consumption is necessary it is not sufficient to induce clinically relevant liver damage in the absence of a secondary risk factor. Studies in rodent models and alcoholic patients show that increased intestinal permeability to microbial products like endotoxin play a critical role in promoting liver inflammation in ALD pathogenesis. Therefore identifying mechanisms of alcohol-induced intestinal permeability is important in identifying mechanisms of ALD and for designing new avenues for therapy. Cyp2e1 is a cytochrome P450 enzyme that metabolizes alcohol has been shown to be upregulated by chronic alcohol use and to be a major source of oxidative stress and liver injury in alcoholics and in animal and in vitro models of chronic alcohol use. Because Cyp2e1 is also expressed in the intestine and is upregulated by chronic alcohol use, we hypothesized it could play a role in alcohol-induced intestinal hyperpermeability. Our in vitro studies with intestinal Caco-2 cells and in mice fed alcohol showed that circadian clock proteins CLOCK and PER2 are required for alcohol-induced permeability. We also showed that alcohol increases Cyp2e1 protein and activity but not mRNA in Caco-2 cells and that an inhibitor of oxidative stress or siRNA knockdown of Cyp2e1 prevents the increase in CLOCK or PER2 proteins and prevents alcohol-induced hyperpermeability. With our collaborators we have also shown that Cyp2e1 knockout mice are resistant to alcohol-induced gut leakiness and liver inflammation. Taken together our data support a novel Cyp2e1-circadian clock protein mechanism for alcohol-induced gut leakiness that could provide new avenues for therapy of ALD.

Indexed as

AnimalsCircadian ClocksCircadian RhythmCytochrome P-450 CYP2E1EthanolFatty Liver, AlcoholicHumansIntestinal MucosaOxidative StressPermeabilityCytochrome P-450 CYP2E1EthanolAlcoholAlcoholic steatohepatitisCircadian rhythmsCyp2e1Intestinal permeability

Identifiers

PMID25462064
PMCPMC4297927
OpenAlexW2069540241

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.