Evidence map›Paper›PMID 36497049›Full record

ArticleCells2022

Efficacy of Clinically Used PARP Inhibitors in a Murine Model of Acute Lung Injury.

Vanessa Martins, Sidneia S Santos, Larissa de O C P Rodrigues, Reinaldo Salomao, Lucas Liaudet, Csaba Szabo

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024
    Review
  6. Review
  7. Article
  8. 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

6 authors at 3 institutions in 2 countries.

Vanessa MartinsSection of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.ORCID 0000-0001-6935-290X
Sidneia S SantosSection of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.
Larissa de O C P RodriguesSection of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.
Reinaldo SalomaoDivision of Infectious Diseases, Department of Medicine, Escola Paulista de Medicina, Federal University of São Paulo (EPM/UNIFESP), São Paulo 04023, Brazil.ORCID 0000-0003-1149-4598
Lucas LiaudetService of Adult Intensive Care Medicine, University Hospital Medical Center, Lausanne University, 1015 Lausanne, Switzerland.
Csaba SzaboSection of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.ORCID 0000-0003-3110-4235
University of Fribourg · CHUniversidade Federal de São Paulo · BRUniversity of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1), as a potential target for the experimental therapy of acute lung injury (ALI), was identified over 20 years ago. However, clinical translation of this concept was not possible due to the lack of clinically useful PARP inhibitors. With the clinical introduction of several novel, ultrapotent PARP inhibitors, the concept of PARP inhibitor repurposing has re-emerged. Here, we evaluated the effect of 5 clinical-stage PARP inhibitors in oxidatively stressed cultured human epithelial cells and monocytes in vitro and demonstrated that all inhibitors (1-30 µM) provide a comparable degree of cytoprotection. Subsequent in vivo studies using a murine model of ALI compared the efficacy of olaparib and rucaparib. Both inhibitors (1-10 mg/kg) provided beneficial effects against lung extravasation and pro-inflammatory mediator production-both in pre- and post-treatment paradigms. The underlying mechanisms include protection against cell dysfunction/necrosis, inhibition of NF-kB and caspase 3 activation, suppression of the NLRP3 inflammasome, and the modulation of pro-inflammatory mediators. Importantly, the efficacy of PARP inhibitors was demonstrated without any potentiation of DNA damage, at least as assessed by the TUNEL method. These results support the concept that clinically approved PARP inhibitors may be repurposable for the experimental therapy of ALI.

Indexed as

Acute Lung InjuryPoly(ADP-ribose) Polymerase InhibitorsAnimalsDisease Models, AnimalHumansInflammation MediatorsLungMiceNecrosisInflammation MediatorsPoly(ADP-ribose) Polymerase Inhibitorscell deathcytokinesinflammationolaparib

Identifiers

PMID36497049
PMCPMC9738530
OpenAlexW4310211229

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.