Evidence map›Paper›PMID 26354996›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

Elevated glutathione is not sufficient to protect against doxorubicin-induced nuclear damage in heart in multidrug resistance-associated protein 1 (Mrp1/Abcc1) null mice.

Jun Deng, Donna Coy, Wei Zhang, Manjula Sunkara, Andrew J Morris, Chi Wang, Luksana Chaiswing, Daret St Clair, Mary Vore, Paiboon Jungsuwadee

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

Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

7 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradationThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020
    Article
  3. Intrauterine Programming of Diabetes Induced Cardiac Embryopathy.Diabetes & obesity international journal · 2019
    Article
  4. Article
  5. Article
  6. Loss of Mrp1 Potentiates Doxorubicin-Induced Cytotoxicity in Neonatal Mouse Cardiomyocytes and Cardiac Fibroblasts.Toxicological sciences : an official journal of the Society of Toxicology · 2016
    Article
  7. 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

10 authors at 3 institutions in 1 country.

Jun DengDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Donna CoyDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Wei ZhangDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Manjula SunkaraDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Andrew J MorrisDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Chi WangDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Luksana ChaiswingDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Daret St ClairDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.).
Mary VoreDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.) maryv@email.uky.edu paiboon@fdu.edu.
Paiboon JungsuwadeeDepartment of Toxicology and Cancer Biology (J.D., D.C., L.C., W.Z., D.St.C., M.V.), Division of Cardiovascular Medicine (M.S., A.J.M.), Markey Cancer Center (C.W.) University of Kentucky, Lexington, Kentucky; Department of Pathology and Laboratory Medicine, William S. Middleton Memorial Veterans Administration Hospital and University of Wisconsin Medical School, Madison Wisconsin (L.C.); and School of Pharmacy, Fairleigh Dickinson University, Florham Park, New Jersey (P.J.) maryv@email.uky.edu paiboon@fdu.edu.
Fairleigh Dickinson University · USUniversity of Kentucky · USWilliam S. Middleton Memorial Veterans Hospital · US

Funding

Vascular Mechanisms of PCB-Induced Brain MetastasesP42ES007380 · NIEHS · UNIVERSITY OF KENTUCKY · PI PEARSON, KEVIN JOSEPH · 1997 to 2024
$47.8M
University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3M
The role of IKKß in linking obesity to adipose tissue inflammation and adipogeneP20GM103527 · NIGMS · UNIVERSITY OF KENTUCKY · PI CASSIS, LISA A · 2012 to 2017
$13.7M
THROMBOSPONDIN1 MEDIATES MACROPHAGE INFILTRATION INTO ADIPOSE TISSUE AND PROMOTEP20RR021954 · NCRR · UNIVERSITY OF KENTUCKY · PI ECKHARDT, ERIK · 2008 to 2011
$8.3M
The role of MRP1 in Protection of Cardiac InjuryR01CA139844 · NCI · UNIVERSITY OF KENTUCKY · PI VORE, MARY · 2008 to 2012
$1.3M
NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA139844NCI NIH HHS R01CA139844NCRR NIH HHS P20 RR021954NIEHS NIH HHS P42 ES007380NIGMS NIH HHS P20 GM103527
6 · The paper itself

Abstract

Cardiotoxicity is a major dose-limiting adverse effect of doxorubicin (DOX), mediated in part by overproduction of reactive oxygen species and oxidative stress. Abcc1 (Mrp1) mediates the efflux of reduced and oxidized glutathione (GSH, GSSG) and is also a major transporter that effluxes the GSH conjugate of 4-hydroxy-2-nonenal (HNE; GS-HNE), a toxic product of lipid peroxidation formed during oxidative stress. To assess the role of Mrp1 in protecting the heart from DOX-induced cardiac injury, wild-type (WT) and Mrp1 null (Mrp1(-/-)) C57BL/6 littermate mice were administered DOX (15 mg/kg) or saline (7.5 ml/kg) i.v., and heart ventricles were examined at 72 hours. Morphometric analysis by electron microscopy revealed extensive injuries in cytosol, mitochondria, and nuclei of DOX-treated mice in both genotypes. Significantly more severely injured nuclei were observed in Mrp1(-/-) versus WT mice (P = 0.031). GSH and the GSH/GSSG ratio were significantly increased in treatment-naïve Mrp1(-/-) versus WT mice; GSH remained significantly higher in Mrp1(-/-) versus WT mice after saline and DOX treatment, with no changes in GSSG or GSH/GSSG. GS-HNE, measured by mass spectrometry, was lower in the hearts of treatment-naïve Mrp1(-/-) versus WT mice (P < 0.05). DOX treatment decreased GS-HNE in WT but not Mrp1(-/-) mice, so that GS-HNE was modestly but significantly higher in Mrp1(-/-) versus WT hearts after DOX. Expression of enzymes mediating GSH synthesis and antioxidant proteins did not differ between genotypes. Thus, despite elevated GSH levels in Mrp1(-/-) hearts, DOX induced significantly more injury in the nuclei of Mrp1(-/-) versus WT hearts.

Indexed as

AnimalsAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsCardiotoxicityCell NucleusDoxorubicinGlutathioneGlutathione DisulfideLipid PeroxidationMice, Inbred C57BLMice, KnockoutMyocardiumOxidative StressAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsDoxorubicinGlutathioneGlutathione Disulfideglutathionyl 4-hydroxy-2-nonenal conjugatemultidrug resistance-associated protein 1

Identifiers

PMID26354996
PMCPMC4613962
OpenAlexW1861006531

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.