Evidence map›Paper›PMID 33179104›Full record

ArticleMolecular medicine reports2021

Reoxygenation induces reactive oxygen species production and ferroptosis in renal tubular epithelial cells by activating aryl hydrocarbon receptor.

Theodoros Eleftheriadis, Georgios Pissas, Georgios Filippidis, Vassilios Liakopoulos, Ioannis Stefanidis

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

Article in Molecular medicine reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 41 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

5 authors at 1 institution in 1 country.

Theodoros EleftheriadisDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.
Georgios PissasDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.
Georgios FilippidisDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.
Vassilios LiakopoulosDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.
Ioannis StefanidisDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.
University of Thessaly · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During the reperfusion phase of ischemia‑reperfusion injury, reactive oxygen species (ROS) production aggravates the course of many diseases, including acute kidney injury. Among the various enzymes implicated in ROS production are the enzymes of the cytochromes P450 superfamily (CYPs). Since arylhydrocarbon receptor (AhR) controls the expression of certain CYPs, the involvement of this pathway was evaluated in reperfusion injury. Because AhR may interact with the nuclear factor erythroid 2‑related factor 2 (Nrf2) and the hypoxia‑inducible factor‑1α (HIF‑1α), whether such an interaction takes place and affects reperfusion injury was also assessed. Proximal renal proximal tubular epithelial cells were subjected to anoxia and subsequent reoxygenation. At the onset of reoxygenation, the AhR inhibitor CH223191, the HIF‑1α activator roxadustat, or the ferroptosis inhibitor α‑tocopherol were used. The activity of AhR, Nrf2, HIF‑1α, and their transcriptional targets were assessed with western blotting. ROS production, lipid peroxidation and cell death were measured with colorimetric assays or cell imaging. Reoxygenation induced ROS production, lipid peroxidation and cell ferroptosis, whereas CH223191 prevented all. Roxadustat did not affect the above parameters. Reoxygenation activated AhR and increased CYP1A1, while CH223191 prevented both. Reoxygenation with or without CH223191 did not alter Nrf2 or HIF‑1α activity. Thus, AhR is activated during reoxygenation and induces ROS production, lipid peroxidation and ferroptotic cell death. These detrimental effects may be mediated by AhR‑induced CYP overexpression, while the Nrf2 or the HIF‑1α pathways remain unaffected. Accordingly, the AhR pathway may represent a promising therapeutic target for the prevention of reperfusion injury.

Indexed as

alpha-TocopherolAnimalsAzo CompoundsBasic Helix-Loop-Helix ProteinsCell HypoxiaCells, CulturedCytochrome P-450 CYP1A1Epithelial CellsFerroptosisGlycineHypoxia-Inducible Factor 1, alpha SubunitIsoquinolinesKidney Tubules, ProximalLipid PeroxidationMiceModels, Biological2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amideAhr protein, mousealpha-TocopherolAzo CompoundsBasic Helix-Loop-Helix ProteinsCyp1a1 protein, mouseCytochrome P-450 CYP1A1GlycineHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitIsoquinolinesNfe2l2 protein, mouseNF-E2-Related Factor 2OxygenPyrazolesReactive Oxygen SpeciesReceptors, Aryl Hydrocarbonroxadustatarylhydrocarbon receptorcytochrome p450ferroptosishypoxia‑inducible factorischemia‑reperfusion injurynuclear factor erythroid2‑related factor 2

Identifiers

PMID33179104
PMCPMC7684866
OpenAlexW3102881732

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.