Cardioprotective effect of dexrazoxane during treatment with doxorubicin: A study using low-dose dobutamine stress echocardiography

Paiva, Marcelo Goulart; Petrilli, Antônio Sérgio; Moisés, Valdir Ambrósio; Macedo, Carla Renata Donato Pacheco; Tanaka, Cristiana; Campos, Orlando

doi:10.1002/pbc.20488

Cited by 31 publications

(21 citation statements)

References 45 publications

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“…This effect has previously been seen, both in patients treated with doxorubicin and in laboratory animals models (Liu et al, 2002;Paiva et al, 2005;Li et al, 2006). It could represent a limitation of the interpretation of the physiological data as the measurement of LV function parameters before and during treatment can be influenced by numerous factors, such as abnormal heart rate, abnormal loading conditions, the presence of cytokine-mediated myocardial depressants, anemic syndrome, infiltration of the myocardium with blasts, sympathetic overdrive, and hyperkinetic circulation.…”

Section: Discussionmentioning

confidence: 94%

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Kogan

Schlesinger²,

Peters³

et al. 2007

J Pharmacol Exp Ther

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Several quinones have been found to be effective in the treatment of some forms of cancer; however, their cumulative heart toxicity limits their use. The cannabinoid quinone HU-331 [3S,4R-pbenzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl] is highly effective against tumor xenografts in nude mice. We report now a comparison of the anticancer activity of HU-331 and its cardiotoxicity with those of doxorubicin in vivo. General toxicity was assayed in Sabra, nude and SCID-NOD mice. The anticancer activity in vivo was assessed by measurement of the tumors with an external caliper in HT-29 and Raji tumor-bearing mice and by weighing the excised tumors. Left ventricular function was evaluated with transthoracic echocardiography. Myelotoxicity was evaluated by blood cell count. Cardiac troponin T (cTnT) plasma levels were determined by immunoassay. HU-331 was found to be much less cardiotoxic than doxorubicin. The control and the HU-331-treated groups gained weight, whereas the doxorubicintreated group lost weight during the study. In HT-29 colon carcinoma, the tumor weight in the HU-331-treated group was 54% smaller than in the control group and 30% smaller than in the doxorubicin-treated group. In Raji lymphoma, the tumor weight in the HU-331-treated group was 65% smaller than in the control group and 33% smaller than in the doxorubicin-treated group. In contrast to doxorubicin, HU-331 did not generate reactive oxygen species in mice hearts (measured by protein carbonylation levels and malondialdehyde levels). In vivo, HU-331 was more active and less toxic than doxorubicin and thus it has a high potential for development as a new anticancer drug.

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Section: Discussionmentioning

confidence: 94%

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Kogan

Schlesinger²,

Peters³

et al. 2007

J Pharmacol Exp Ther

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“…Dexrazoxane plays an important role in the cardioprotection of patients treated with anthracycline derivatives [11,24]. It is indeed well recognized that these derivatives can induce various histological lesions of the heart, such as myocardial Table 1 Incidence and severity of histologic cardiac lesions observed in rabbits at the end of a 3-month treatment with saline, testosterone, testosterone plus trimetazidine, or testosterone plus dexrazoxane via the intraperitoneal route The severity of changes was assessed semi-quantitatively and is denoted: (0) no changes; (x) mild changes; (xx) moderate changes; (xxx) marked changes; (xxxx) severe changes necrosis, cellular infiltrates, myofibrillar loss, and cytoplasmic vacuolization.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine

et al. 2009

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Further to our previous observation of post-mortem cardiac lesions after sudden death in several athletes with a history of anabolic steroid abuse, this study was intended to reproduce these lesions in rabbits administered testosterone oenanthate, a prototypic anabolic steroid abused by athletes, and to provide evidence for the protective effects of trimetazidine and dexrazoxane that are used as antianginal and cardioprotective drugs, respectively. Groups of six rabbits each were administered saline, testosterone, or a combination of testosterone and either trimetazidine or dexrazoxane for 3 months. Histologic cardiac lesions including necrosis, misshapen cell nuclei, interstitial and endocardial fibrosis, lymphocytic infiltrates, and vascular dystrophies were observed in testosterone-treated rabbits. In contrast, no significant lesions were observed in the animals treated with testosterone combined with either trimetazidine or dexrazoxane. This is the first study providing evidence for testosterone cardiotoxicity following sub-chronic exposure in laboratory animals. In addition, these results suggest the protective role of trimetazidine and dexrazoxane.

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“…Es ist noch nicht ganz klar, wie der Wirkungsmechanismus ist, jedoch haben mehrere Studien gezeigt, dass Dexrazoxan die Kardiotoxizität von Anthracyclinen um 70-80% verringern kann. Einziges Caveat bleibt die Unsicherheit bezüglich einer eventuellen Reduktion der Antitumoreffizienz der Anthracycline oder eine mögliche Erhöhung der Inzidenz von Sekundär-malignomen [50][51][52][53][54][55][56][57][58][59][60]. Es sind jedoch weitere Studien notwendig, um diese vorläufigen Ergebnisse zu untermauern.…”

Section: Präventionunclassified

Chemotherapeutikainduzierte Herzinsuffizienz

Paulides

Wojnowski²

2007

Med Klin

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Cardioprotective effect of dexrazoxane during treatment with doxorubicin: A study using low-dose dobutamine stress echocardiography

Abstract: Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only, suggesting less cardiotoxicity.

Cited by 31 publications

References 45 publications

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine

Chemotherapeutikainduzierte Herzinsuffizienz

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