Characterisation of a Cellular Model of Cardiomyopathy, in the Rabbit, Produced by Chronic Administration of the Anthracycline, Epirubicin

Kelso, Elizabeth; Geraghty, Robert F.; McDermott, Barbara; Cameron, C. H. S.; Nicholls, D. P.; Silke, Bernard

doi:10.1006/jmcc.1997.0563

Cited by 15 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rabbit studies, in which hypertrophy was induced also by combined aortic insufficiency and constriction, I Ca,L density was also found to be unchanged in hypertrophied myocytes compared with Ctrl myocytes [32,33]. Unchanged I Ca,L was also found in the hypertrophy model of rabbits with renovascular hypertension [34] and epirubicin-induced cardiomyopathy [35], but a decrease of I Ca,L density was found in rapid pacing induced heart failure in rabbit [36], although this is not a consistent finding [37].…”

Section: Ca 2+ Currentmentioning

confidence: 92%

Etiology-dependency of ionic remodeling in cardiomyopathic rabbits

Verkerk

Baartscheer

Groot

et al. 2011

International Journal of Cardiology

View full text Add to dashboard Cite

Section: Ca 2+ Currentmentioning

confidence: 92%

Etiology-dependency of ionic remodeling in cardiomyopathic rabbits

Verkerk

Baartscheer

Groot

et al. 2011

International Journal of Cardiology

View full text Add to dashboard Cite

“…Their use, however, is limited by the risk of a delayed, life-threatening and irreversible form of dilatory congestive heart failure, with a mortality that exceeds 50% within 2 years [3][4][5]. Mechanistically, anthracycline-induced cardiomyopathy involves the generation of free radicals [6][7][8][9][10] and selective inhibition of cardiac-specific genes involved in cardiac development and function, such as CARP and SERCA2 [11][12][13], leading to extensive cardiomyocyte apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Cardiac safety and antitumoral activity of a new nitric oxide derivative of pegylated epirubicin in mice

et al. 2007

View full text Add to dashboard Cite

The use of epirubicin is limited by the risk of a dilatory congestive heart failure that develops as a consequence of induction of a mitochondrial-dependent cardiomyocyte apoptosis. In a previous in-vitro study, we have provided evidence that a new formulation of pegylated epirubicin- bearing moieties that release nitric oxide, named BP-747, exerted a potent antitumoral activity against a colon cancer cell line, which was completely devoid of cytotoxic activity against cardiomyocytes. The aim of this study was to investigate the antitumoral and cardiotoxic profile of BP-747 in Caco-2 and SKOV-2 tumor-bearing mice. Epirubicin-induced cardiomyopathy was detected by clinical (survival, weight loss), anatomical (heart weight loss) and biochemical evaluations (measurement of serum troponin and creatine phosphokinase levels). The antitumoral activity was investigated by the measurement of tumor diameters and weight. In comparison with free epirubicin and pegylated epirubicin, BP-747 showed more potent antineoplastic effects, as demonstrated by the 95% reduction of tumor volume. Moreover, while administration of epirubicin and pegylated epirubicin resulted in the development of a severe anthracycline cardiomyopathy, BP-747-treated mice were virtually devoid of clinical and biochemical signs of cardiotoxicity. The present data provide evidence that addition of a nitric oxide-releasing moiety to pegylated epirubicin confers a new and unique cytotoxic profile to the drug.

show abstract

“…Although EPI-induced cardiotoxicity occurs at higher cumulative doses (>900 mg/m 2 ) compared with doxorubicin (>500 mg/m 2 ), chronic and irreversible myocardial damage leading to congestive heart failure increases abruptly with higher cumulative doses (5)(6)(7). Cellular mechanisms of EPI-induced myocardial damage are similar to that of doxorubicin and involve a mitochondria-dependent apoptosis of cardiomyocytes (8)(9)(10)(11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Nitric oxide modulates proapoptotic and antiapoptotic properties of chemotherapy agents: the case of NO‐pegylated epirubicin

et al. 2006

View full text Add to dashboard Cite

The use of the anthracycline epirubicin (EPI) is limited by the risk of a dilatory congestive heart failure that develops as a consequence of induction of a mitochondrial-dependent cardiomyocyte and endothelial cell apoptosis. Nitric oxide (NO) increases the antitumoral activity of several chemotherapics, while it provides protection against apoptosis induced by oxidative stress both in endothelial cells and cardiomyocytes. The aim of the present study was to investigate whether the addition of an NO-releasing moiety to a pegylated derivative of EPI (p-EPI-NO) confers to the drug a different cytotoxic profile against tumoral and normal cells. The cytotoxic profile of the drugs was investigated in Caco-2 cell line, in embryonic rat heart-derived myoblasts (H9c2), in adult cardiomyocytes, and in endothelial cells (HUVEC). p-EPI-NO was more efficient than EPI in inducing Caco-2 cell apoptosis, while it spared HUVEC, H9c2 cells and adult cardiomyocytes from EPI-induced toxicity. Exposure of cells to p-EPI-NO resulted in a NO-mediated inhibition of cellular respiration followed by mitochondrial membrane depolarization and cell death in Caco-2 cells but not in HUVEC and H9c2 cells in which mitochondrial membrane polarization was maintained at the expense of glycolytically generated ATP. These findings indicate that addition of an NO-releasing moiety to p-EPI increases the anti-neoplastic activity of the drug, while it reduces its cytotoxicity against nonneoplastic cells.

show abstract

Characterisation of a Cellular Model of Cardiomyopathy, in the Rabbit, Produced by Chronic Administration of the Anthracycline, Epirubicin

Cited by 15 publications

References 0 publications

Etiology-dependency of ionic remodeling in cardiomyopathic rabbits

Etiology-dependency of ionic remodeling in cardiomyopathic rabbits

Cardiac safety and antitumoral activity of a new nitric oxide derivative of pegylated epirubicin in mice

Nitric oxide modulates proapoptotic and antiapoptotic properties of chemotherapy agents: the case of NO‐pegylated epirubicin

Contact Info

Product

Resources

About