Adriamycin-induced cardiomyopathy can serve as a model for diabetic cardiomyopathy – a hypothesis

Renu, Kaviyarasi; Abilash, V G; Pichiah, P.B. Tirupathi; Syeda, Thabassum Akthar; Arunachalam, Sankarganesh

doi:10.1016/j.apjtb.2017.09.021

Cited by 12 publications

(10 citation statements)

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“…The objective of the present study was to assess the possible pro- has been restricted due to cardiomyopathy induced by cardiotoxicity. [29,54,55] Several mechanisms of DIC have been proposed; however, enhanced OS and subsequent mitochondrial dysfunction are among the major contributors to DOX-induced cardiac damage. [7,8] In the present study, DOX-induced toxicity in experimental mice was evidenced by significant body weight loss.…”

Section: Discussionmentioning

confidence: 99%

“…DOX is used for the treatment of several types of human cancers, although its clinical use has been restricted due to cardiomyopathy induced by cardiotoxicity. [ 29,54,55 ] Several mechanisms of DIC have been proposed; however, enhanced OS and subsequent mitochondrial dysfunction are among the major contributors to DOX‐induced cardiac damage. [ 7,8 ]…”

Section: Discussionmentioning

confidence: 99%

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Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Abu-Khudir

Ibrahim

Shams

et al. 2021

J Biochem & Molecular Tox

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Clinically, the use of doxorubicin (DOX) is limited due to DOX-induced cardiotoxicity (DIC). The current study aimed to evaluate the cardioprotective effect of trehalose (TRE) against DIC in a female Swiss albino mouse model. Mice were divided into five experimental groups: Gp. I: saline control group (200 μl/mouse saline three times per week for 3 weeks day after day), Gp. II: DOX-treated group (2 mg/kg body weight three times per week for 3 weeks day after day), Gp. III: TRE group (200 μg/mouse three times per week for 3 weeks day after day), Gp. IV: DOX + TRE cotreatment group (animals were coadministered with DOX and TRE as in Gp. II and III, respectively), and Gp. V: DOX + TRE posttreatment group (animals were treated with DOX as in Gp. II followed by treatment with TRE as in Gp. III). DOX-treated mice showed significant elevation in cardiac injury biomarkers (lactate dehydrogenase, creatine kinase isoenzyme-MB, and cardiac troponin I), cardiac oxidative stress (OS) markers (malondialdehyde and myeloperoxidase), and cardiac levels of autophagyrelated protein 5. Moreover, DOX significantly reduced the levels of total antioxidant capacity and activities of catalase and glutathione S-transferase.In contrast, TRE treatment of DOX-administered mice significantly improved almost all of the above-mentioned assessed parameters. Furthermore, histopathological changes of cardiac tissues observed in mice treated with TRE in combination with DOX were significantly improved as compared to DOXtreated animals. Taken together, the present study provides evidence that TRE has cardioprotective effects against DIC, which is likely mediated via suppression of OS and autophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Abu-Khudir

Ibrahim

Shams

et al. 2021

J Biochem & Molecular Tox

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“…In our earlier investigations, we had demonstrated that the dysregulation of lipid metabolism occurs due to alterations in PPARγ and Klf4 to be one of the major pathological components in Adriamycin-induced cardiomyopathy. This dysregulation is also mimicked in diabetic cardiomyopathy. , However, very few reports are present in terms of cardiac repair and remodeling mechanisms. Adriamycin-induced cardiomyopathy has been shown to be reversed by embryonic stem cells and induced pluripotent stem cells injected into mouse heart, which showed induction of Notch signaling and reversed the effect .…”

Section: Discussionmentioning

confidence: 99%

“…In our earlier investigations, we had demonstrated that the dysregulation of lipid metabolism occurs due to alterations in PPARγ and Klf4 to be one of the major pathological components in Adriamycin-induced cardiomyopathy. This dysregulation is also mimicked in diabetic cardiomyopathy. − Since Klf4 is one of the four pluripotent factors having a role in differentiation of cells such as goblet cells and also proves to regulate embryogenesis through formation of hatching cells, we believe that Klf4 might play a protective role in the heart upon any insult. However, studies show that Notch1 signaling plays an upstream regulation over Klf4 in goblet cells differentiation; hence, we deduced to explore its role in heart cells in the presence of Adriamycin.…”

Section: Introductionmentioning

confidence: 93%

Paeonol Reverses Adriamycin Induced Cardiac Pathological Remodeling through Notch1 Signaling Reactivation in H9c2 Cells and Adult Zebrafish Heart

Iqbal

Pichiah

Sudhakaran

et al. 2019

Chem. Res. Toxicol.

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Adriamycin is a commonly prescribed chemotherapeutic drug for a wide range of cancers. Adriamycin causes cardiotoxicity as an adverse effect that limits its clinical application in cancer treatment. Several mechanisms have been proposed to explain the toxicity it causes in heart cells. Disruption of inherent cardiac repair mechanism is the least understood mechanism of Adriamycin-induced cardiotoxicity. Adriamycin induces pathological remodeling in cardiac cells by promoting apoptosis, hypertrophy, and fibrosis. We found that Adriamycin inhibited Notch1 in a time- and dose-dependent manner in H9c2 cells. We used Paeonol, a Notch1 activator, and analyzed the markers of apoptosis, hypertrophy, and fibrosis in H9c2 cells in vitro and in adult zebrafish heart in vivo as model systems to study Adriamycin-induced cardiotoxicity. Paeonol activated Notch1 signaling and expression of its downstream target genes effectively in the Adriamycin-treated condition in vitro and in vivo. Also we detected that Notch activation using Paeonol protected the cells from apoptosis, collagen deposition, and hypertrophy response using functional assays. We conclude that Adriamycin induced cardiotoxicity by promoting the pathological cardiac remodeling through inhibition of Notch1 signaling and that the Notch1 reactivation by Paeonol protected the cells and reversed the cardiotoxicity.

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“…), belong to natural and semi‐synthetic anthraquinones and have antitumor effect. Despite the fact that the use of AB is accompanied by a wide range of organotoxic effects [1,2] , these anticancer agents still remain the «first line» drugs in the treatment of various tissue sarcomas, breast cancer and small cell lung cancer, as well as blastomas arising from hematopoietic system cells. In recent decades, in order to reduce side effects and to overcome drug resistance of tumor cells, researchers have been actively synthesizing various derivatives of AB with natural compounds of various classes [3–5] .…”

Section: Introductionmentioning

confidence: 99%

New Conjugates of Daunorubicin with Sesquiterpene Lactones and Their Biological Activity

et al. 2021

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New conjugates of daunorubicin with sesquiterpene lactones at the 3′‐amino group of anthracycline were synthesized and their effect on the viability of cell lines (HL60, Jurkat, K562, and A549) was assessed using a resazurin test. The effect on the cell cycle and apoptosis by flow cytometry was studied. The following natural lactones were used for modification: telekin, isotelekin, reynosin, costunolide, dehydrocostuslactone, santamarine and epoxyisoalantolactone. The synthesized conjugates are characterized by a general high toxicity (8…0.14 μM) in relation to tumor cell lines (in some cases, higher than the toxicity of the initial antibiotic), as well as a comparable effect on the cell cycle (arrest in the G2/M‐phase) with a relatively low the effect on the initiation of apoptosis at concentrations close to the IC50.

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Adriamycin-induced cardiomyopathy can serve as a model for diabetic cardiomyopathy – a hypothesis

Cited by 12 publications

References 61 publications

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Paeonol Reverses Adriamycin Induced Cardiac Pathological Remodeling through Notch1 Signaling Reactivation in H9c2 Cells and Adult Zebrafish Heart

New Conjugates of Daunorubicin with Sesquiterpene Lactones and Their Biological Activity

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