Time course of cardiomyopathy induced by doxorubicin in rats

Medeiros-Lima, Daniel J M; Carvalho, Jorge José de; Tibiriçá, Eduardo; Borges, Juliana Pereira; Matsuura, Cristiane

doi:10.1016/j.pharep.2019.02.013

Cited by 16 publications

(17 citation statements)

References 30 publications

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“…R. glutinosa also displays antiaging properties by exerting protective effects on the cardiovascular and vascular systems. Catalpol, an iridoid glycoside isolated from the roots of R. glutinosa, has been reported to display neuroprotective effects (38,39). Previous studies have also demonstrated the cardioprotective and anti-inflammatory properties of catalpol, including apoptosis inhibition, reduced neuronal death and promotion of differentiation (40,41).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, DOX induces cardiomyocyte damage when it destroys tumor cells ( 4 ). Early myocardial damage manifests as myocarditis and arrhythmia; however, when DOX reaches a specific dose, irreversible myocardial expansion occurs, which may eventually develop into heart failure ( 38 ). Although numerous efforts have been made to reduce the toxicity of DOX, no significant progress in the prevention and treatment of DOX-induced toxicity has been reported.…”

Section: Discussionmentioning

confidence: 99%

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Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Jiang

Zhang

2020

Exp Ther Med

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Drug-induced cardiomyopathy is a severe disease that leads to refractory heart disease at late stages, with increasing detrimental effects. DOX-induced cell damage is primarily induced via cellular oxidative stress. The present study investigated the effects of catalpol on doxorubicin (DOX)-induced H9C2 cardiomyocyte inflammation and oxidative stress. The Cell Counting Kit-8 assay was performed to detect cell viability, and western blotting was performed to detect the expression of peroxisome proliferator-activated receptor (PPAR)-γ in H9C2 cells. The expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were measured using ELISAs. Furthermore, the oxidative stress kit was used to detect the levels of malondialdehyde, superoxide dismutase and glutathione peroxidase. A reactive oxygen species (ROS) kit and DCF-DA staining were used to detect ROS levels. The results indicated that DOX treatment inhibited H9C2 cell expression of PPAR-γ and decreased H9C2 cell viability. Various concentrations of catalpol exhibited a less potent effect on H9C2 cell viability compared with DOX; however, catalpol increased the viability of DOX-induced H9C2 cells. Catalpol treatment also significantly decreased the expression levels of inflammatory factors (TNF-α, IL-1β and IL-6) in DOX-induced H9C2 cells, which was reversed by transfections with short hairpin RNA targeting PPAR-γ. Results from the present study indicated that catalpol ameliorated DOX-induced inflammation and oxidative stress in H9C2 cardiomyoblasts by activating PPAR-γ.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Jiang

Zhang

2020

Exp Ther Med

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“…Other short-term models use 2–3.4 mg/kg of DOX every other day, six times intraperitoneally (the total dose is 12–20 mg/kg) ( Zbinden et al, 1978 ; Lanza et al, 1989 ; Carvalho et al, 2010 ; Razmaraii et al, 2016 ; Cappetta et al, 2018 ; Aygun and Gul, 2019 ; Barış et al, 2019 ). Long-term rat models typically use 1–5 mg/kg every week for 2–12 weeks with a cumulative dose of 3–25 mg/kg ( Villani et al, 1991 ; Sacco et al, 2001 ; Sayed-Ahmed et al, 2001 ; Rahimi Balaei et al, 2010 ; Hydock et al, 2012 ; Hole et al, 2013 ; Toblli et al, 2014 ; Kang et al, 2017 ; Medeiros-Lima et al, 2019 ; Wang et al, 2019 ; Chakouri et al, 2020 ; Sharma et al, 2020 ). Thus, a short-term high-dose injection model would be suitable for assessing acute cardiotoxicity, while a long-term low-dose model would be suitable for assessing chronic cardiotoxicity.…”

Section: Anthracycline Cardiomyopathy Modelsmentioning

confidence: 99%

“…Histological examination showed that this injection protocol results in irregularly spaced myocardial fibers with inflammation, edema, and leukocyte cell infiltration. Other models use 1 mg/kg of DOX for 10 days and 1.25 mg/kg of DOX 4 times a week for 4 weeks ( Medeiros-Lima et al, 2019 ; Aykan et al, 2020 ). The results show that DOX significantly reduced body, heart and left ventricular weight one week after stopping DOX.…”

Section: Anthracycline Cardiomyopathy Modelsmentioning

confidence: 99%

Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

et al. 2021

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Today the pharmacological possibilities of treating cancer are expanding and as a result, life expectancy is increasing against the background of chemotherapy and supportive treatment. In the conditions of successful antitumor treatment, complications associated with its toxic effect on healthy tissues and organs began to come to the fore. Anthracycline cardiomyopathy was the first serious cardiovascular complication to draw the attention of oncologists and cardiologists around the world. Anthracycline drugs such as doxorubicin, epirubicin, idarubicin are still widely used in oncological practice to treat a wide range of solid and hematological malignancies. Doxorubicin-induced cardiomyopathy is closely associated with an increase in oxidative stress, as evidenced by reactive oxygen species (ROS) nduced damage such as lipid peroxidation, and decreased levels of antioxidants. Myofibrillar destruction and dysregulation of intracellular calcium are also important mechanisms, usually associated with doxorubicin-induced cardiotoxicity. Despite the abundance of data on various mechanisms involved in the implementation of doxorubicin-induced cardiotoxicity, a final understanding of the mechanism of the development of doxorubicin cardiomyopathy has not yet been formed. It poses the most significant challenges to the development of new methods of prevention and treatment, as well as to the unambiguous choice of a specific treatment regimen using the existing pharmacological tools. In order to resolve these issues new models that could reflect the development of the chemotherapy drugs effects are needed. In this review we have summarized and analyzed information on the main existing models of doxorubicin cardiomyopathy using small laboratory animals. In addition, this paper discusses further areas of research devoted to the development and validation of new improved models of doxorubicin cardiomyopathy suitable both for studying the mechanisms of its implementation and for the preclinical drugs effectiveness assessment.

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“…Irrespective of its cause, cardiomyocyte injury by itself triggers an inflammatory reaction, which also induces fibroblast activation [6][7][8][9].. In anthracycline-induced cardiomyopathy, both inflammatory and adverse ECM remodeling processes are present [4,[10][11][12][13][14]. Several transcriptomic analysis in animal and in vitro studies have reported differential expression in genes related to the innate immune system, TGFß signaling, and collagen turnover [10,[15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis

et al. 2021

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As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1–8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.

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Time course of cardiomyopathy induced by doxorubicin in rats

Cited by 16 publications

References 30 publications

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Catalpol ameliorates doxorubicin‑induced inflammation and oxidative stress in H9C2 cells through PPAR‑γ activation

Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis

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