Evidence map›Paper›PMID 33574047›Full record

ArticleMolecular pharmacology2021

Elevated cAMP Protects against Diclofenac-Induced Toxicity in Primary Rat Hepatocytes: A Protective Effect Mediated by the Exchange Protein Directly Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Factors.

Fabio Alejandro Aguilar Mora, Nshunge Musheshe, Asmaa Oun, Manon Buist-Homan, Frank Lezoualc'h, Xiaodong Cheng, Martina Schmidt, Han Moshage

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

Article in Molecular pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 12 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

8 authors at 1 institution in 3 countries.

Fabio Alejandro Aguilar MoraDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Nshunge MushesheDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Asmaa OunDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).ORCID 0000-0003-4486-5914
Manon Buist-HomanDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Frank Lezoualc'hDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Xiaodong ChengDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Martina SchmidtDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.).
Han MoshageDept. Gastroenterology and Hepatology (F.A.A.M., M.B.-H., H.M.), Dept. Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD, GRIAC (N.M., A.O., M.S.), Dept. Laboratory Medicine (M.B.-H., H.M.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Inserm UMR-1048, Institut des Maladies Métaboliques et Cardiovasculaires, Univ Toulouse Paul Sabatier, Toulouse, France (F.L.); and Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, Texas (X.C.) a.j.moshage@umcg.nl.
University Medical Center Groningen · NL

Funding

Exchange Protein directly Activated by cAMP (EPAC): Structure, Function and TherapeuticsR35GM122536 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI CHENG, XIAODONG · 2017 to 2021
$1.9M
NIGMS NIH HHS R35 GM122536
6 · The paper itself

Abstract

Chronic consumption of the nonsteroidal anti-inflammatory drug diclofenac may induce drug-induced liver injury (DILI). The mechanism of diclofenac-induced liver injury is partially elucidated and involves mitochondrial damage. Elevated cAMP protects hepatocytes against bile acid-induced injury. However, it is unknown whether cAMP protects against DILI and, if so, which downstream targets of cAMP are implicated in the protective mechanism, including the classic protein kinase A (PKA) pathway or alternative pathways like the exchange protein directly activated by cAMP (EPAC). The aim of this study was to investigate whether cAMP and/or its downstream targets protect against diclofenac-induced injury in hepatocytes. Rat hepatocytes were exposed to 400 µmol/l diclofenac. Apoptosis and necrosis were measured by caspase-3 activity assay and Sytox green staining, respectively. Mitochondrial membrane potential (MMP) was measured by JC-10 staining. mRNA and protein expression were assessed by quantitative polymerase chain reaction (qPCR) and Western blot, respectively. The cAMP-elevating agent 7

Indexed as

AnimalsAnti-Inflammatory Agents, Non-SteroidalCyclic AMPDiclofenacGuanine Nucleotide Exchange FactorsHEK293 CellsHepatocytesHumansMaleRatsRats, WistarAnti-Inflammatory Agents, Non-SteroidalCyclic AMPDiclofenacGuanine Nucleotide Exchange FactorsRapgef3 protein, ratRapgef4 protein, rat

Identifiers

PMID33574047
PMCPMC11033960
OpenAlexW3126350940

What OpenQuestion holds

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Registered trials

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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.