Evidence map›Paper›PMID 26727525›Full record

ArticleAlcoholism, clinical and experimental research2016

Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity.

P S S Rao, Santosh Kumar

Open access · greenAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2016. 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
2.5field-weighted citation impact, top 11% 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, 29 citations in OpenAlex.

  1. Review
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  3. Review
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  8. Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells.International journal of molecular sciences · 2021
    Article
  9. Review
  10. Review
  11. Article
  12. Article
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  17. Molecular Basis of Alcohol-Related Gastric and Colon Cancer.International journal of molecular sciences · 2017
    Review
  18. Article
  19. Article
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

2 authors at 1 institution in 1 country.

P S S RaoPharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
Santosh KumarPharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
University of Tennessee Health Science Center · US

Funding

Role of cytochrome P450 in alcohol-mediated effects on antiretroviral and HIV-1R01AA022063 · NIAAA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KUMAR, SANTOSH · 2013 to 2017
$1.7M
NIAAA NIH HHS AA022063NIAAA NIH HHS R01 AA022063
6 · The paper itself

Abstract

backgroundOur recent study has shown that acute treatment with ethanol (EtOH) increases oxidative stress and cytotoxicity through cytochrome P450 2E1 (CYP2E1)-mediated pathway in U937 monocytic cells. U937 cells are derived from blood monocytes and are considered as the model system for HIV-related study. Since the prevalence of alcohol use in HIV-infected population is high, and HIV+ patients are on antiretroviral therapy (ART) soon after they are diagnosed, it is important to study the interactions between EtOH and ART in monocytes.

methodsThis study examined the chronic effects of EtOH and ART (darunavir/ritonavir), alone and in combination, on expression/levels of cytochrome P450 enzymes (CYPs), antioxidant enzymes (AOEs), reactive oxygen species (ROS), and cytotoxicity in U937 cells. The mRNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. ROS and cytotoxicity were measured using flow cytometry and cell viability assay, respectively.

resultsWhile chronic ART treatment increased CYP2E1 protein expression by 2-fold, EtOH and EtOH+ART increased CYP2E1 by ~5-fold. In contrast, ART and EtOH treatments decreased CYP3A4 protein expression by 38 ± 17% and 74 ± 15%, respectively, and the combination additively decreased CYP3A4 level by 90 ± 8%. Expressions of superoxide dismutase 1 (SOD1) and peroxiredoxin (PRDX6) were decreased by both EtOH and ART, however, the expressions of SOD2 and catalase were unaltered. These results suggested increased EtOH metabolism, increased ART accumulation, and decreased defense against ROS. Therefore, we determined the effects of EtOH and ART on ROS and cytotoxicity. While ART showed a slight increase, EtOH and EtOH+ART displayed significant increase in ROS and cytotoxicity. Moreover, the combination showed additive effects on ROS and cytotoxicity.

conclusionsThese results suggest that chronic EtOH, in the absence and presence of ART, increases ROS and cytotoxicity in monocytes, perhaps via CYP- and AOE-mediated pathways. This study has clinical implications in HIV+ alcohol users who are on ART.

Indexed as

AntioxidantsBlotting, WesternCatalaseCell LineCell SurvivalCentral Nervous System DepressantsCytochrome P-450 CYP2E1Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDarunavirEthanolHIV Protease InhibitorsHumansMonocytesOxidative StressPeroxiredoxin VIAntioxidantsCatalaseCentral Nervous System DepressantsCytochrome P-450 CYP2E1Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDarunavirEthanolHIV Protease InhibitorsPeroxiredoxin VIPRDX6 protein, humanRitonavirRNA, MessengerSOD1 protein, humanSuperoxide DismutaseSuperoxide Dismutase-1Superoxide Dismutase 2Antioxidant EnzymesCytochrome P450sDarunavir/RitonavirEthanolOxidative Stress

Identifiers

PMID26727525
PMCPMC4700550
OpenAlexW2222954109

What OpenQuestion holds

Textmetadata
LicenceTDM
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.