Evidence map›Paper›PMID 29084443›Full record

ArticleAntioxidants & redox signaling2018

SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress.

Patricia Rada, Virginia Pardo, Maysa A Mobasher, Irma García-Martínez, Laura Ruiz, Águeda González-Rodríguez, Cristina Sanchez-Ramos, Jordi Muntané, Susana Alemany, Laura P James and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Antioxidants & redox signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.

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20 more citing papers are in PubMed but not listed here.

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

14 authors at 5 institutions in 4 countries.

Patricia Rada1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Virginia Pardo1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Maysa A Mobasher1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Irma García-Martínez1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Laura Ruiz1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Águeda González-Rodríguez4 Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Princesa , Madrid, Spain .
Cristina Sanchez-Ramos1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Jordi Muntané5 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid, Spain .
Susana Alemany1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Laura P James7 Section of Clinical Pharmacology and Toxicology, Arkansas Children's Hospital , Little Rock, Arkansas.
Kenneth J Simpson8 Division of Clinical and Surgical Sciences, University of Edinburgh , Edinburgh, United Kingdom .
María Monsalve1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Maria Pilar Valdecantos1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Ángela M Valverde1 Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid, Spain .
Consejo Superior de Investigaciones Científicas · ESArkansas Children's Hospital · USHospital Universitario Santa Cristina · ESInstituto de Salud Carlos III · ESUniversity of Edinburgh · GB

Funding

Adduct Dipstick for Diagnosis of Acetaminophen ToxicityR42DK079387 · NIDDK · ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC · PI JAMES, LAURA PHILLIPS · 2011 to 2018
$4.4M
NIDDK NIH HHS R42 DK079387
6 · The paper itself

Abstract

aimsSirtuin 1 (SIRT1) is a key player in liver physiology and a therapeutic target against hepatic inflammation. We evaluated the role of SIRT1 in the proinflammatory context and oxidative stress during acetaminophen (APAP)-mediated hepatotoxicity.

resultsSIRT1 protein levels decreased in human and mouse livers following APAP overdose. SIRT1-Tg mice maintained higher levels of SIRT1 on APAP injection than wild-type mice and were protected against hepatotoxicity by modulation of antioxidant systems and restrained inflammatory responses, with decreased oxidative stress, proinflammatory cytokine messenger RNA levels, nuclear factor kappa B (NFκB) signaling, and cell death. Mouse hepatocytes stimulated with conditioned medium of APAP-treated macrophages (APAP-CM) showed decreased SIRT1 levels; an effect mimicked by interleukin (IL)1β, an activator of NFκB. This negative modulation was abolished by neutralizing IL1β in APAP-CM or silencing p65-NFκB in hepatocytes. APAP-CM of macrophages from SIRT1-Tg mice failed to downregulate SIRT1 protein levels in hepatocytes. In vivo administration of the NFκB inhibitor BAY 11-7082 preserved SIRT1 levels and protected from APAP-mediated hepatotoxicity. INNOVATION: Our work evidenced the unique role of SIRT1 in APAP hepatoprotection by targeting oxidative stress and inflammation.

conclusionSIRT1 protein levels are downregulated by IL1β/NFκB signaling in APAP hepatotoxicity, resulting in inflammation and oxidative stress. Thus, maintenance of SIRT1 during APAP overdose by inhibiting NFκB might be clinically relevant. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16:293-296, 2012) with the following serving as open reviewers: Rafael de Cabo, Joaquim Ros, Kalervo Hiltunen, and Neil Kaplowitz. Antioxid. Redox Signal. 28, 1187-1208.

Indexed as

AcetaminophenAnimalsCell DeathCells, CulturedHumansInflammationLiverMacrophagesMaleMiceMice, Inbred C57BLOxidative StressRAW 264.7 CellsSirtuin 1AcetaminophenSirt1 protein, mouseSirtuin 1antioxidant defensehepatotoxicityinflammationinterleukin 1βoxidative stressparacetamolSIRT1

Identifiers

PMID29084443
PMCPMC9545809
OpenAlexW2765656723

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.