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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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Doxorubicin (DOX) is used as a chemotherapeutic agent in the treatment of solid tumors. Irreversible cardiotoxicity is the major limitation in the clinical use of DOX. Several microRNAs (miRNAs) with diversified functions are identified that participate in exacerbating or suppressing DOX-induced cardiac damage. The miRNAs are small noncoding regulatory RNAs that modify the expression of the native genes. Studies have demonstrated that miRNAs by modifying the expression of proteins such as PTEN, Akt, and survivin can affect DOX-induced cardiac apoptosis. Moreover, miRNAs can modulate cardiac oxidative stress in DOX treatment through the posttranscriptional regulation of Sirt1, p66shc, and Nrf2 expressions. This manuscript has reviewed the regulation of the PI3K/Akt/p53 and the Sirt1/Nrf2 pathways by miRNAs in DOX-induced cardiotoxicity., (© 2022 Wiley Periodicals LLC.)

Objectives: Doxorubicin (DOX) is widely prescribed for the treatment of several human cancers. Unfortunately, cumulative doses of DOX are the main cause of myocardial dysfunction. Although preclinical and pharmaceutical studies were performed to investigate the potential of natural compounds in minimizing DOX toxicity, a comprehensive review of them is not available. This review can help the researchers for an effective search strategy., Key Findings: Oxidative stress and p53 play an important role in DOX-associated cardiotoxicity. DOX activates nicotinamide adenine dinucleotide phosphate NADPH oxidase (NOX) in the heart, resulting in excessive reactive oxygen species that can induce cardiomyocyte apoptosis through phosphorylation of p53, DNA damage and/or mitogen-activated protein kinases-mediated cardiomyocyte apoptosis. Although a few chemical drugs with high efficacy are administered along with DOX to prevent or more likely to reduce cardiovascular toxicity, their use is often limited by additional side effects. Recently, attention has been drawn to natural compounds that prevent DOX cardiotoxicity. This review focuses on some of the natural bioactive compounds with potential therapeutic efficacy against DOX-induced cardiotoxicity (DIC)., Summary: Some natural compounds, especially flavonols, flavonoids and proanthocyanidins, have the most protective effects against DIC by forming stable radicals and preventing the assembly of the NOX subunits., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Doxorubicin (DOX) is a potent chemotherapeutic agent; however, the accompanying cardiotoxicity is a significant complication of the usefulness of treatment with DOX. Multiple mechanisms have been suggested for this often fatal side effect, one of which is inflammation. Several pathways with different targets have been reported to result in DOX-induced heart inflammation. Some natural occurring compounds (NCs) have been reported to interact with the DOX-induced cardiotoxicity through targeting one or more of several pathways, including the Nrf2/NF-kB, TLR-4/NF-kB, MAPK/NF-kB, and NLRP3 inflammasome pathways. This article reviews several of these pathways and the potential protective effect of some NCs against the cardiac inflammation induced by DOX., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiotoxicity is a major adverse effect that can be induced by both therapeutic agents and industrial chemicals. The pathogenesis of such cardiac damage is multifactorial, often injuring the cardiac tissue by generating free radicals, oxidative stress, and/or inflammation. Curcumin (CUR) is a bright yellow chemical produced by Curcuma longa plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family, Zingiberaceae. Administration of CUR has been reported to ameliorate the chemical and drug-induced cardiac injury in several studies. CUR has been suggested to act as an effective candidate against oxidative stress and inflammation in heart tissue via regulation of Nrf2 and suppression of p38 MAPK/NF-κB and NLRP3 inflammasomes. The anti-apoptotic properties of CUR have also been reported to modulate the AMPK, Akt, JNK, and ERK signaling pathways. This review explores the potential protective effects of CUR regarding the detrimental effects often observed in cardiac tissue following exposure to several chemicals including drugs.

Cardiotoxicity is the main concern for long-term use of the doxorubicin (DOX). Reactive oxygen species (ROS) generation leads to oxidative stress that significantly contributes to the cardiac damage induced by DOX. The nuclear factor erythroid 2-related factor (Nrf2) acts as a protective player against DOX-induced myocardial oxidative stress. Several natural compounds (NCs) with anti-oxidative effects, were examined to suppress DOX cardiotoxicity such as asiatic acid, α-linolenic acid, apigenin, baicalein, β-lapachone, curdione, dioscin, ferulic acid, Ganoderma lucidum polysaccharides, genistein, ginsenoside Rg3, indole-3-carbinol, naringenin-7-O-glucoside, neferine, p-coumaric acid, pristimerin, punicalagin, quercetin, sulforaphane, and tanshinone IIA. The present article, reviews NCs that showed protective effects against DOX-induced cardiac injury through induction of Nrf2 signaling pathway., (© 2020 John Wiley & Sons Ltd.)

Cardiotoxicity is a critical concern in the use of several cytotoxic drugs. Induction of apoptosis, inflammation, and autophagy following dysregulation of the PI3K/Akt signaling pathway contributes to the cardiac damage induced by these drugs. Several natural compounds (NCs), including ferulic acid, gingerol, salvianolic acid B, paeonol, apigenin, calycosin, rutin, neferine, higenamine, vincristine, micheliolide, astragaloside IV, and astragalus polysaccharide, have been reported to suppress cytotoxic drug-induced cardiac injury. This article reviews these NCs that have been reported to have a protective effect against cytotoxic drug-induced cardiotoxicity through regulation of the PI3K/Akt signaling pathway., (© 2020 Wiley Periodicals LLC.)

Doxorubicin (DOX) is a chemotherapeutic agent with marked, dose-dependent cardiotoxicity that leads to tachycardia, atrial and ventricular arrhythmia, and irreversible heart failure. Induction of the endoplasmic reticulum (ER) which plays a major role in protein folding and calcium homeostasis was reported as a key contributor to cardiac complications of DOX. This article reviews several chemical compounds that have been shown to regulate DOX-induced inflammation, apoptosis, and autophagy via inhibition of ER stress signaling pathways, such as the IRE1α/ASK1/JNK, IRE1α/JNK/Beclin-1, and CHOP pathways., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA), an estrogenic compound, is used in manufacture of polycarbonate plastics and epoxy resins. Curcumin, the active ingredient of turmeric, is a potent protective compound against cardiac diseases. In this study the protective effect of nanomicelle curcumin on BPA-induced subchronic cardiotoxicity in rats was evaluated. Rats were divided into 6 groups including control, nanomicelle curcumin (50 mg/kg, gavage), BPA (50 mg/kg, gavage), nanomicelle curcumin (10, 25, and 50 mg/kg) plus BPA. The treatments were continued for 4 weeks. Results revealed that BPA significantly induced histophatological injuries including focal lymphatic inflammation, nuclear degenerative changes and cytoplasmic vacuolation, increased body weight, systolic and diastolic blood pressures, malondialdehyde and Creatine phosphokinase-MB level and decreased glutathione content in comparison with control group. In addition, in electrocardiographic graph, RR, QT, and PQ intervals were increased by BPA. Western blot analysis showed that BPA up-regulated phosphorylated p38 (p38-mitogen-activated protein kinase) and JNK (c-jun NH 2 terminal kinases), while down-regulated phosphorylated AKT (Protein Kinase B) and ERK1/2 (extracellular signal-regulated protein kinases 1 and 2). However, nanomicelle curcumin (50 mg/kg) significantly improved these toxic effects of BPA in rat heart tissue. The results provide evidence that nanomicelle curcumin showed preventive effects on subchronic exposure to BPA induced toxicity in the heart tissue in rats., (© 2018 Wiley Periodicals, Inc.)

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant and its toxicity is mediated by the aryl hydrocarbon receptor (AHR). Mechanisms of TCDD cardiovascular toxicity consist of oxidative stress, growth factor modulation, and ionic current alteration. It is indicated that the rodent cardiovascular system is a target for TCDD cardiomyopathy. Here, our understanding of TCDD cardiovascular toxicity is reviewed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Although doxorubicin (DOX) is among the most widely used anticancer agents, its clinical application is hampered owing to its cardiotoxicity. Adjuvant therapy with an antioxidant has been suggested as a promising strategy to reduce DOX-induced adverse effects. In this context, many phenolic compounds have been reported to protect against DOX-induced cardiotoxicity. The cardioprotective effects of phenolic compounds are exerted via multiple mechanisms including inhibition of reactive oxygen species generation, apoptosis, NF-κB, p53, mitochondrial dysfunction, and DNA damage. In this review, we present a summary of the in vitro, in vivo, and clinical findings on the protective mechanisms of phenolic compounds against DOX-induced cardiotoxicity.

Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre‐treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As‐mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down‐regulated autophagy markers such as Beclin‐1 expression and the LC3‐II/I ratio. Moreover, the cardiac expression of cleaved‐caspase‐3 and Bax/Bcl‐2 ratio was decreased by Mel pretreatment. Reduced expression of miR‐34a and miR‐144 by As were reversed by Mel. The histopathological changes of cardiac injury associated with As exposure was moderated by Mel. Mel may improve As‐induced cardiac dysfunction through anti‐oxidative, anti‐apoptotic, and anti‐autophagic mechanisms. [ABSTRACT FROM AUTHOR]

Cardiotoxicity can be a complication of both drugs and a variety of other chemicals that affects morbidity, quality of life, and even mortality. The accumulation of lipids and inflammation have been implicated in the development of cardiotoxicity. The peroxisome proliferator-activated receptors (PPARs), a family of transcription factors, have a role in controlling the cardiac expression of genes involved in lipid and glucose metabolism and the inflammatory response. The different PPAR isoforms, PPARα, PPARγ, and PPARβ/δ, have a role in multiple functions in cardiac tissue. The protective nature of several naturally occurring chemicals (NCs) against cardiotoxicity by targeting PPARα and PPARγ has been reported. The literature related to the ability of several NCs to modulate cardiotoxicity through targeting the AMP-activated protein kinase (AMPK)/the PPARγ coactivator-1 alpha (PGC-1α)/PPARα, the PPARα/the nuclear factor-kappa B (NF-κB), and the PPARγ/the nuclear factor-erythroid 2 related factors 2 (Nrf2)/the heme oxygenase-1 (HO-1)/NF-κB signaling pathways are reviewed. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a potent antitumor agent with a broad spectrum of activity; however, irreversible cardiotoxicity resulting from DOX treatment is a major issue that limits its therapeutic use. Sirtuins (SIRTs) play an essential role in several physiological and pathological processes including oxidative stress, apoptosis, and inflammation. It has been reported that SIRT1 and SIRT3 can act as a protective molecular against DOX‐induced myocardial injury through targeting numerous signaling pathways. Several natural compounds (NCs), such as resveratrol, sesamin, and berberine, with antioxidative, anti‐inflammation, and antiapoptotic effects were evaluated for their potential to suppress the cardiotoxicity induced by DOX via targeting SIRT1 and SIRT3. Numerous NCs exerted their therapeutic effects on DOX‐mediated cardiac damage via targeting different signaling pathways, including SIRT1/LKB1/AMPK, SIRT1/PGC‐1α, SIRT1/NLRP3, and SIRT3/FoxO. SIRT3 also ameliorates cardiotoxicity by enhancing mitochondrial fusion. [ABSTRACT FROM AUTHOR]

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities. [ABSTRACT FROM AUTHOR]

Cardiac disorders remain one of the most important causes of death in the world. Oxidative stress has been suggested as one of the molecular mechanisms involved in drug-induced cardiac toxicity. Recently, several natural products have been utilized in different studies with the aim to protect the progression of oxidative stress-induced cardiac disorders. There is a large body of evidence that administration of antioxidants may be useful in ameliorating cardiac toxicity. Silymarin, a polyphenolic flavonoid has been shown to have utility in several cardiovascular disorders. In this review, various studies in scientific databases regarding the preventive effects of silymarin against cardiotoxicity induced by chemicals were introduced. Although there are many studies representing the valuable effects of silymarin in different diseases, the number of researches relating to the possible cardiac protective effects of silymarin against drugs induced toxicity is rather limited. Results of these studies show that silymarin has a broad spectrum of cardiac protective activity against toxicity induced by some chemicals including metals, environmental pollutants, oxidative agents and anticancer drugs. Further studies are needed to establish the utility of silymarin in protection against cardiac toxicity. [ABSTRACT FROM AUTHOR]

Arsenic, a naturally ubiquitous element, is found in foods and environment. Cardiac dysfunction is one of the major causes of morbidity and mortality in the world. Arsenic exposure is associated with various cardiopathologic effects including ischemia, arrhythmia and heart failure. Possible mechanisms of arsenic cardiotoxicity include oxidative stress, DNA fragmentation, apoptosis and functional changes of ion channels. Several evidences have shown that mitochondrial disruption, caspase activation, MAPK signaling and p53 are the pathways for arsenic induced apoptosis. Arsenic trioxide is an effective and potent antitumor agent used in patients with acute promyelocytic leukemia and produces dramatic remissions. As 2 O 3 administration has major limitations such as T wave changes, QT prolongation and sudden death in humans. In this review, we discuss the underlying pathobiology of arsenic cardiotoxicity and provide information about cardiac health effects associated with some medicinal plants in arsenic toxicity. [ABSTRACT FROM AUTHOR]

Nano-particles (NPs) are used in industrial and biomedical fields such as cosmetics, food additives and biosensors. Beside their favorable properties, nanoparticles are responsible for toxic effects. Local adverse effects and/or systemic toxicity are described with nanoparticle delivery to target organs of the human body. Animal studies provide evidence for the aforementioned toxicity. Cardiac function is a specific target of nanoparticles. Thus, reviewing the current bibliography on cardiotoxicity of nanoparticles and specifically of titanium, zinc, silver, carbon, silica and iron oxide nano-materials is the aim of this study. [ABSTRACT FROM AUTHOR]