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Molecular mechanisms involved in doxorubicin-induced cardiotoxicity: A bibliometrics analysis by VOSviewer

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Abstract

Doxorubicin is a potent chemotherapeutic agent that can cause cardiotoxicity. Many documents (more than 14,000) have been published in the area of doxorubicin-induced cardiotoxicity (DIC) since 1970. A comprehensive bibliographic analysis of author keywords was used to describe better and understand the molecular mechanisms involved in DIC. The objective was to consider the state of the author keywords of research on the molecular mechanisms involved in DIC based on a bibliometrics study of articles published over the past fifty years. A bibliometrics analysis was conducted using VOSviewer with data collected from the Web of Science Core Collection database of over 14,000 documents (from 1970 to July 19, 2023). Using scientific publications retrieved about DIC, author keywords were assessed at the scientific field level. The current study showed that the annual number of DIC-related publications has increased over the past 50 years. The Journal of Clinical Oncology is the leading journal in this field. The top cited DIC document was published in 2004. The top keywords with high frequency were "doxorubicin," "cardiotoxicity," and "adriamycin." According to the results of this study, the most common mechanisms involved in DIC were as follows oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis. The highest occurrences of regulators-related author keywords were "AKT," "Sirt1," and "AMPK.” Based on the findings, oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis were hot research mechanisms of DIC from 1970 to July 19, 2023.

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Abbreviations

AMPK:

AMP-activated protein kinase

ATF6:

Activating transcription factor 6

Bax:

Bcl-2-associated X protein

Bcl-2:

B-cell lymphoma 2

DIC:

Doxorubicin-induced cardiotoxicity

ER:

Endoplasmic reticulum

ERK1/2:

Extracellular-signal-regulated kinase 1 and 2

FoxO3a:

Forkhead box O3

GPx4:

Glutathione peroxidase 4

IRE1α:

Inositol-requiring kinase 1 alpha

JNK:

C-Jun N-terminal kinase

LC3:

Microtubule-associated protein 1A/1B-light chain 3

MAPKs:

Mitogen-activated protein kinases

mTOR:

Mammalian target of rapamycin

NAD:

Nicotinamide adenine dinucleotide

NF-κB:

Nuclear factor-kappa beta

NLRP3:

NLR family pyrin domain containing 3

Nrf2:

Nuclear factor erythroid 2-related factor 2

PDK1:

Phosphoinositide-dependent kinase-1

PERK:

Protein kinase-like ER kinase

PGC-1α:

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha

PI3K:

Phosphoinositide 3‐kinase

PINK1:

PTEN-induced kinase 1

PIP2:

Phosphatidylinositol‐4,5‐bisphosphate

PIP3:

Phosphatidylinositol‐3,4,5‐trisphosphate

SIRTs:

Sirtuins

STAT3:

Signal transducer and activator of transcription 3

TNF-α:

Tumor necrosis factor-alpha

TSC2:

Tuberous sclerosis complex 2

UPR:

Unfolded protein response

WoS:

Web of Science

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Acknowledgements

Authors are grateful to the Kermanshah University of Medical Sciences, Health Technology Institute, Medical Biology Research Center, Kermanshah, Iran for financial support.

Funding

This work was supported by the Kermanshah University of Medical Sciences, Health Technology Institute, Medical Biology Research Center, Kermanshah, Iran.

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GhK conceived and designed research. FY analyzed data. GhK and AWH: Review and Editing. FY wrote the manuscript. All authors read and approved the manuscript. The authors confirm that no paper mill and artificial intelligence was used.

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Correspondence to Gholamreza Karimi.

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The authors declare no competing interests.

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Yarmohammadi, F., Wallace Hayes, A. & Karimi, G. Molecular mechanisms involved in doxorubicin-induced cardiotoxicity: A bibliometrics analysis by VOSviewer. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1971–1984 (2024). https://doi.org/10.1007/s00210-023-02773-2

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