Evidence mapPaperPMID 36773545Full record

ArticleRedox biology2023

Hydropersulfides (RSSH) attenuate doxorubicin-induced cardiotoxicity while boosting its anticancer action.

Blaze M Pharoah, Chengximeng Zhang, Vinayak S Khodade, Gizem Keceli, Christopher McGinity, Nazareno Paolocci, John P Toscano

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  9. Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025
    Review
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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

7 authors at 3 institutions in 2 countries.

Blaze M PharoahDepartment of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
Chengximeng ZhangDepartment of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
Vinayak S KhodadeDepartment of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
Gizem KeceliDivision of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
Christopher McGinityCenter for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States.
Nazareno PaolocciDivision of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: npaoloc1@jhmi.edu.
John P ToscanoDepartment of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States. Electronic address: jtoscano@jhu.edu.
Johns Hopkins University · USNational Cancer Institute · USUniversity of Padua · IT

Funding

Technological Assessment and Solutions Core - RC4P30AG021334 · JOHNS HOPKINS UNIVERSITY · 2003 to 2025
$6.1M
Translational Aging Research Training ProgramT32AG058527 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$612k
NHLBI NIH HHS R01 HL136918NIA NIH HHS P30 AG021334NIA NIH HHS T32 AG058527NIGMS NIH HHS R01 GM145940NIGMS NIH HHS T32 GM080189
6 · The paper itself

Abstract

Cardiotoxicity is a frequent and often lethal complication of doxorubicin (DOX)-based chemotherapy. Here, we report that hydropersulfides (RSSH) are the most effective reactive sulfur species in conferring protection against DOX-induced toxicity in H9c2 cardiac cells. Mechanistically, RSSH supplementation alleviates the DOX-evoked surge in reactive oxygen species (ROS), activating nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways, thus boosting endogenous antioxidant defenses. Simultaneously, RSSH turns on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a master regulator of mitochondrial function, while decreasing caspase-3 activity to inhibit apoptosis. Of note, we find that RSSH potentiate anticancer DOX effects in three different cancer cell lines, with evidence that suggests this occurs via induction of reductive stress. Indeed, cancer cells already exhibit much higher basal hydrogen sulfide (H

Indexed as

CardiotoxicityOxidative StressApoptosisDoxorubicinHumansMyocytes, CardiacReactive Oxygen SpeciesSulfidesDoxorubicinReactive Oxygen SpeciesSulfidesCytoprotectionDoxorubicin-induced cardiotoxicityHydropersulfidesNrf2PGC-1αReductive stress

Identifiers

PMID36773545
PMCPMC9929489
OpenAlexW4319222006

What Socratic 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 Socratic graph.