Evidence map›Paper›PMID 25347994›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

M1 polarization bias and subsequent nonalcoholic steatohepatitis progression is attenuated by nitric oxide donor DETA NONOate via inhibition of CYP2E1-induced oxidative stress in obese mice.

Ratanesh Kumar Seth, Suvarthi Das, Sahar Pourhoseini, Diptadip Dattaroy, Stephen Igwe, Julie Basu Ray, Daping Fan, Gregory A Michelotti, Anna Mae Diehl, Saurabh Chatterjee

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.8field-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

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Targeting hepatic macrophages for non-alcoholic fatty liver disease therapy.Frontiers in cell and developmental biology · 2024
    Review
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  17. Article
  18. Article
  19. Nitric oxide in liver diseases.Trends in pharmacological sciences · 2015
    Review
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

10 authors at 4 institutions in 1 country.

Ratanesh Kumar SethEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Suvarthi DasEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Sahar PourhoseiniEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Diptadip DattaroyEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Stephen IgweEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Julie Basu RayEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Daping FanEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Gregory A MichelottiEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Anna Mae DiehlEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.).
Saurabh ChatterjeeEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina (R.K.S., S.D., S.P., D.D., S.C.); School of Science, Technology, Engineering and Mathematics (STEM), Dillard University, New Orleans, Louisiana (S.I., J.B.R.); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina (D.F.); and Division of Gastroenterology, Duke University, Durham, North Carolina (G.A.M., A.M.D.) schatt@mailbox.sc.edu.
Dillard University · USDuke University · USSouth Carolina Department of Health and Environmental Control · USUniversity of South Carolina · US

Funding

LIVER DISEASE IN OBESITYR01DK053792 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DIEHL, ANNA MAE ELIZABETH · 1999 to 2013
$3.6M
Free Radical Mechanism in Obesity Potentiation of Environmental HepatotoxicityR00ES019875 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI CHATTERJEE, SAURABH · 2012 to 2014
$747k
NIDDK NIH HHS R01 DK053792NIEHS NIH HHS 4R00-ES019875-02NIEHS NIH HHS R00 ES019875
6 · The paper itself

Abstract

Activation of M1 macrophages in nonalcoholic steatohepatitis (NASH) is produced by several external or endogenous factors: inflammatory stimuli, oxidative stress, and cytokines are known. However, any direct role of oxidative stress in causing M1 polarization in NASH has been unclear. We hypothesized that CYP2E1-mediated oxidative stress causes M1 polarization in experimental NASH, and that nitric oxide (NO) donor administration inhibits CYP2E1-mediated inflammation with concomitant attenuation of M1 polarization. Because CYP2E1 takes center stage in these studies, we used a toxin model of NASH that uses a ligand and a substrate of CYP2E1 for inducing NASH. Subsequently, we used a methionine and choline-deficient diet-induced rodent NASH model where the role of CYP2E1 in disease progression has been shown. Our results show that CYP2E1 causes M1 polarization bias, which includes a significant increase in interleukin-1β (IL-1β) and IL-12 in both models of NASH, whereas CYP2E1-null mice or diallyl sulfide administration prevented it. Administration of gadolinium chloride (GdCl3), a macrophage toxin, attenuated both the initial M1 response and the subsequent M2 response, showing that the observed increase in cytokine levels is primarily from macrophages. Based on the evidence of an adaptive NO increase, the NO donor administration in vivo that mechanistically inhibited CYP2E1 catalyzed the oxidative stress during the entire study in NASH-abrogated M1 polarization and NASH progression. The results obtained show the association of CYP2E1 in M1 polarization, and that inhibition of CYP2E1 catalyzed oxidative stress by an NO donor (DETA NONOate [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate]) can be a promising therapeutic strategy in NASH.

Indexed as

Disease ProgressionAnimalsCytochrome P-450 CYP2E1Gene Expression RegulationLipid PeroxidationLiverMacrophagesMaleMiceMice, ObeseNitric Oxide DonorsNitroso CompoundsNon-alcoholic Fatty Liver DiseaseOxidative StressRNA, MessengerTyrosine2,2'-(hydroxynitrosohydrazono)bis-ethanamineCytochrome P-450 CYP2E1Nitric Oxide DonorsNitroso CompoundsRNA, MessengerTyrosine

Identifiers

PMID25347994
PMCPMC4279102
OpenAlexW1974488167

What OpenQuestion holds

Textmetadata
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.