Animal models of anthracycline cardiotoxicity: Basic mechanisms and cardioprotective activity

Herman, Eugene H.; Ferrans, Víctor J.

doi:10.1016/s1058-9813(98)00002-2

Cited by 31 publications

(35 citation statements)

References 30 publications

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“…single injection were observed in the present study which was in correlation to that of Chakrabartia et al [30]. Most of the studies support the view that an increase in oxidative stress evidenced by an increase in free radicals and lipid peroxidation as well as a decrease in antioxidants and sulfahydryl groups play an important role in the pathogenesis of doxorubicin-induced cardiomyopathy [31,32]. Our study demonstrated the presence of apoptotic machinery in terms of caspase-3, to be involved in the cardiotoxicity of doxorubicin.…”

Section: Discussionsupporting

confidence: 91%

Anti-apoptotic potential of rosuvastatin pretreatment in murine model of cardiomyopathy

Sharma

Pathan

Kumar

et al. 2011

International Journal of Cardiology

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Section: Discussionsupporting

confidence: 91%

Anti-apoptotic potential of rosuvastatin pretreatment in murine model of cardiomyopathy

Sharma

Pathan

Kumar

et al. 2011

International Journal of Cardiology

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“…In addition, long-term studies are necessary to more accurately evaluate the actions of potential cardioprotectants. As indicated earlier, antioxidants, such as vitamin E and N -acetylcysteine, were protective in models that used single, high anthracycline doses but were not protective when examined in models where cardiotoxicity was induced by long-term administration of low anthracycline doses 20. Thus, the protective effects of previously identified investigational agents (such as probucol32 or sildenafil33) or other emerging strategies need to be re-evaluated using long-term animal studies that use clinically relevant routes and doses of the drugs.…”

Section: Needed Basic Researchmentioning

confidence: 76%

“…One reason for the uncertainty is the apparent lack of protection provided by antioxidants, such as vitamin E and N -acetylcysteine in long-term experimental and clinical trials 20,21. Although the protective effects of carvedilol, an α1-β1,2-adrenoceptor blocker, were tentatively attributed to its antioxidant properties, confirmation awaits comparisons of carvedilol with other adrenolytic agents without antioxidant properties 22…”

Section: Needed Basic Researchmentioning

confidence: 99%

Anthracycline Cardiotoxicity: From Bench to Bedside

Gianni

Herman

Lipshultz

et al. 2008

JCO

419

331

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Anthracyclines remain among the most widely prescribed and effective anticancer agents. Unfortunately, life-threatening cardiotoxicity continues to compromise their usefulness. Despite more than four decades of investigation, the pathogenic mechanisms responsible for anthracycline cardiotoxicity have not been completely elucidated. In addition, new drugs and combination therapies often exacerbate the toxicity. The First International Workshop on Anthracycline Cardiotoxicity, held in fall 2006, in Como, Italy, focused on the state-of-the-art knowledge and discussed the research needed to address the cardiotoxicity of these drugs. Here, we incorporate these discussions into the framework of a broader review of preclinical and clinical issues.

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“…Finally, we utilized a Sprague-Dawley animal model of cardiotoxicity that exhibits genetic variability and thus less susceptibility to cardiotoxicity after DOX exposure. Other animals including canines,20 non-human primates,20 or mice20 have been shown highly susceptible to DOX and may be useful in future studies.…”

Section: Discussionmentioning

confidence: 99%

Novel Approach to Early Detection of Doxorubicin Cardiotoxicity by Gadolinium-Enhanced Cardiovascular Magnetic Resonance Imaging in an Experimental Model

Lightfoot

D’Agostino

Hamilton

et al. 2010

Circ: Cardiovascular Imaging

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Background-We sought to determine whether cardiovascular magnetic resonance measures of gadolinium (Gd) signal intensity (SI) within the left ventricular myocardium are associated with future changes in left ventricular ejection fraction (LVEF) after receipt of doxorubicin (DOX). Methods and Results-Forty Sprague-Dawley rats were divided into 3 groups scheduled to receive weekly intravenous doses of normal saline (nϭ7), 1.5 mg/kg DOX (nϭ19), or 2.5 mg/kg DOX (nϭ14). Magnetic resonance determinations of LVEF and myocardial Gd-SI were performed before and at 2, 4, 7, and 10 weeks after DOX initiation. During treatment, animals were euthanized at different time points so that histopathologic assessments of the left ventricular myocardium could be obtained. Within-group analyses were performed to examine time-dependent relations between Gd-SI and primary events (deterioration in LVEF or an unanticipated death). Six of 19 animals receiving 1.5 mg/kg DOX and 10 of 14 animals receiving 2.5 mg/kg DOX experienced a primary event; no normal saline animals experienced a primary event. In animals with a primary event, histopathologic evidence of myocellular vacuolization occurred (Pϭ0.04), and the Gd-SI was elevated relative to baseline at the time of the event (PϽ0.0001) and during the measurement period before the event (Pϭ0.0001). In all animals (including normal saline) without an event, measures of Gd-SI did not differ from baseline. Conclusions-After DOX, low serial measures of Gd-SI predict an absence of an LVEF drop or unanticipated death. An increase in Gd-SI after DOX forecasts a subsequent drop in LVEF as well as histopathologic evidence of intracellular vacuolization consistent with DOX cardiotoxicity. (Circ Cardiovasc Imaging. 2010;3:550-558.)

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Animal models of anthracycline cardiotoxicity: Basic mechanisms and cardioprotective activity

Cited by 31 publications

References 30 publications

Anti-apoptotic potential of rosuvastatin pretreatment in murine model of cardiomyopathy

Anti-apoptotic potential of rosuvastatin pretreatment in murine model of cardiomyopathy

Anthracycline Cardiotoxicity: From Bench to Bedside

Novel Approach to Early Detection of Doxorubicin Cardiotoxicity by Gadolinium-Enhanced Cardiovascular Magnetic Resonance Imaging in an Experimental Model

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