Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches

Sheibani, Mohammad; Azizi, Yaser; Shayan, Maryam; Nezamoleslami, Sadaf; Eslami, Faezeh; Farjoo, Mohammad Hadi; Dehpour, Ahmad Reza

doi:10.1007/s12012-022-09721-1

Cited by 86 publications

(58 citation statements)

References 150 publications

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“…Several mechanisms may be responsible for doxorubicin-induced cardiotoxicity. These mechanisms include mitochondrial injury, ROS generation, intracellular Ca+2 dysregulation, inflammatory cytokine production, and myocyte damage ( Rawat et al, 2021 ; Sheibani et al, 2022 ; Wu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats

et al. 2022

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Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum (R.turkestanicum) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity.Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed.Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes.Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.

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Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats

et al. 2022

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“…Although DOXO is the most common chemotherapeutic agent in several malignancies, its use is associated with important cardiac complications, enclosed in the broad definition of “DOXO cardiotoxicity” [ 52 , 53 , 54 , 55 ]. Based on the time of onset, cardiotoxicity may be acute, manifesting within two weeks from the end of treatment; chronic, developing within one year; or late-onset, developing even several years after chemotherapy completion.…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons

Moro

Dokshokova

Vanaja

et al. 2022

IJMS

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Doxorubicin (DOXO) remains amongst the most commonly used anti-cancer agents for the treatment of solid tumors, lymphomas, and leukemias. However, its clinical use is hampered by cardiotoxicity, characterized by heart failure and arrhythmias, which may require chemotherapy interruption, with devastating consequences on patient survival and quality of life. Although the adverse cardiac effects of DOXO are consolidated, the underlying mechanisms are still incompletely understood. It was previously shown that DOXO leads to proteotoxic cardiomyocyte (CM) death and myocardial fibrosis, both mechanisms leading to mechanical and electrical dysfunction. While several works focused on CMs as the culprits of DOXO-induced arrhythmias and heart failure, recent studies suggest that DOXO may also affect cardiac sympathetic neurons (cSNs), which would thus represent additional cells targeted in DOXO-cardiotoxicity. Confocal immunofluorescence and morphometric analyses revealed alterations in SN innervation density and topology in hearts from DOXO-treated mice, which was consistent with the reduced cardiotropic effect of adrenergic neurons in vivo. Ex vivo analyses suggested that DOXO-induced denervation may be linked to reduced neurotrophic input, which we have shown to rely on nerve growth factor, released from innervated CMs. Notably, similar alterations were observed in explanted hearts from DOXO-treated patients. Our data demonstrate that chemotherapy cardiotoxicity includes alterations in cardiac innervation, unveiling a previously unrecognized effect of DOXO on cardiac autonomic regulation, which is involved in both cardiac physiology and pathology, including heart failure and arrhythmias.

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“…Doxorubicin (Dox) is one of the most widely used anthracycline anti-cancer drugs for the treatment of solid tumors (such as prostate cancer, ovarian cancer, breast cancer, and gastrointestinal cancer). However, these anti-cancer drugs have various side effects, such as allergic reactions, heart injuries, hair loss, bone marrow suppression, vomiting, and bladder stimulation, which limit their clinical application [ 19 ]. In order to reduce or even eliminate the toxicity and side effects of Dox, scientists have undertaken a series of efforts.…”

Section: Aptamer–drug Delivery Systems Against Prostate Cancermentioning

confidence: 99%

Insights into Aptamer–Drug Delivery Systems against Prostate Cancer

Wang

Qian

et al. 2022

Molecules

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Prostate cancer is a common cancer in elderly males. Significant progress has been made in the drug therapies for prostate cancer in recent years. However, side effects are still problems that have not been overcome by the currently used anti-prostate cancer drugs. Novel technologies can be applied to reduce or even eliminate the side effects of drugs. An aptamer may be a sequence of nucleic acids or peptides that can specifically recognize proteins or cells. Taking advantage of this feature, scientists have designed aptamer–drug delivery systems for the development of anti-prostate cancer agents. Theoretically, these aptamer–drug delivery systems can specifically recognize prostate cancer cells and then induce cell death without attacking normal cells. We collected the relevant literature in this field and found that at least nine compounds have been prepared as aptamer–drug delivery systems to evaluate their precise anti-prostate cancer effects. However, the currently studied aptamer–drug delivery systems have not yet entered the market due to defects. Here, we analyze the published data, summarize the characteristics of these delivery systems, and propose ways to promote their application, thus promoting the development of the aptamer–drug delivery systems against prostate cancer.

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Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches

Cited by 86 publications

References 150 publications

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats

Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons

Insights into Aptamer–Drug Delivery Systems against Prostate Cancer

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