Cardiac Toxicity of Daunorubicin

Bonadonna, Gianni; Monfardini, S.; Marmont, A; Damasio, E; Rossi, F

doi:10.1016/s0140-6736(69)92093-5

Cited by 171 publications

(45 citation statements)

References 7 publications

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“…Doxorubicin (DOX) is one of the most active anthracycline antibiotics that has been used for long time in the therapy of many types of human malignancies [1], [2] either alone or combination with other cytocidal agents [3]. Its clinical uses are limited by seriously high incidence of cardiotoxicity, acute effects can occur immediately after treatment and are characterized by transient arrhythmias, reversible hypotension and pericarditis [4] while, chronic cardiotoxicity can manifest years to decades after treatment.…”

Section: Introductionmentioning

confidence: 99%

Effects of caffeic acid on doxorubicin induced cardiotoxicity in rats

Mohammad¹,

Aharis²,

Yousif³

et al. 2013

AJBM

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Doxorubicin (Dox) is one of the most potent broad-spectrum antitumor anthracycline antibiotics, its use is limited by the development of life-threatening cardiomyopathy.Doxorubicin generates free radicals and induces oxidative stress associated with cellular injury. Further, it has been shown that free radicals are involved in doxorubicin-induced toxicity. The goal of this study is to investigated the cardio-protective effects of caffeic acid on doxorubicin induced cardiotoxicity. The rats were randomized into three equal groups, sham group without treatment, doxorubicin treated group at a dose 3mg/kg IP every other two days and group treated with doxorubicin plus caffeic acid 40mg/day. Two weeks later LV function measurment were performed and blood samples were collected from the heart to measurment plasma levels of cardiac troponin-I (cTn-I), oxidative stress parameter malondialdehyde (MDA) and high a sensitive c-reactive protein (hs-CRP). The hearts were excised for cardiac tissue cytokines (TNF-α, IL-1β, IL-10) measurement and microscopic examination. Rats in the Dox+caffeic acid group had improved LV function, reduced cytokine expression, decreased myocardial marker injury (cTn-I) and less MDA, hs-CRP levels in comparison with the Dox group. Pathological finding appeared nearly normal in the Dox+caffeic acid without fibrosis. The results of the present study reveal that caffeic acid has a promising cardioprotective effect against doxorubicin-induced cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Effects of caffeic acid on doxorubicin induced cardiotoxicity in rats

Mohammad¹,

Aharis²,

Yousif³

et al. 2013

AJBM

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“…Since their introduction in the 1960s it has been well recognised that anthracyclines cause cardiac toxicity. [3] The anti-neoplastic effect of anthracyclines is achieved via their inhibition of DNA synthesis, transcription and replication, however using iron as a co-factor they also generate reactive oxygen species (ROS) which directly damage protein, lipids and DNA causing oxidative stress. Since cardiomyocytes have lower levels of free radical scavenging systems they are more sensitive to ROS induced injury.…”

Section: Introductionmentioning

confidence: 99%

Adolescent survivor of childhood Acute Myeloid Leukaemia undertakes pregnancy with a severe anthracycline induced cardiomyopathy and risk taking behaviours

Tripaydonis

Conyers

2016

CRIM

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A 16-year-old female survivor of childhood Acute Myeloid Leukaemia (AML) presented 12 weeks pregnant to her haematology oncology late effects appointment. Having failed to attend recent healthcare appointments her severe cardiomyopathy secondary to chemotherapy during childhood was poorly managed and she had missed the opportunity to discuss her reproductive plans and have her periconceptional care delivered. This case emphasises the challenges in engaging Adolescent and Young Adult-aged (AYA-aged) cancer survivors with their healthcare and the importance of narrative medicine, adequate health literacy and early transition to adult services for improved medical care.

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“…However, it is being recognized that other mechanisms, including the generation of free radical intermediates ( 5 , 6) and possibly bioreductive covalent attachment to biomolecules, may also be significant (7). These agents suffer from two serious disadvantages: ( i ) a tendency to undergo reductive deglycosidation to produce the inactive 7-deoxyaglycones (1,2), and (ii) a severe dose-related cardiotoxicity (8,9). Evidence has accumulated to indicate that both effects require 'Studies related to antitumor antibiotics, Part XXVI.…”

Section: Introductionmentioning

confidence: 99%

Electron paramagnetic resonance characterization and conformation of daunorubicin semiquinone intermediate implicated in anthracycline metabolism, cardiotoxicity, and anticancer action

Lown¹,

Chen²

1981

Can. J. Chem.

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The antitumor antibiotic daunorubicin, upon reduction in aqueous solution. gives a transient resolved epr spectrum of linewidth 17.OG and g value of 2.0024. This is ascribed to the semiquinone previously tentatively assigned in the unresolved epr spectrum obtained by microsomal activation of the antibiotic. By reference to the epr spectrum of quinizarin semiquinone in aqueous solution the individual proton hyperfine splitting constants in both spectra were tentatively assigned by computer simulation. LCAO-MC! calculations of one-electron wave function spin densities in both species gave good agreement between calculated and observed hfs for values of the parameters Pc,/PCc = 1.8, Fa = 1.4, allowing definite assignment of the aromatic protons. By considering the angular dependence of the ring A benzylic proton hfs it was possible to discriminate between two alternative half-chair conformations of daunorubicin semiquinone. The preferred conformation of the intermediate is tentatively assigned as that which places both 7 and 9 oxygen functions equatorial and the C-9 acetyl group axial.J. WILLIAM LOWN et HSIAO-HSIUNG CHEN. Can. J . Chem. 59, 3212 (1981). L a reduction en solution aqueuse de la daunorubicine, un antibiotique antitumoral, permet d'observer un spectre de rpe d'un compose transitoire presentant une largeur de bandes de 17.0 G et avec une valeur de g de 2.0024. On attribue ceci a la semiquinone dont on avait suppose anterieurement I'existence en se basant sur un spectre de rpe non resolu obtenu par activation microsomique d e I'antibiotique. En se referant au spectre de rpe de la semiquinone de la quinizarine en solution aqueuse et d'une simulation par ordinateur. on a attribue d'une fagon preliminaire les constantes de couplage hyperfin. Les calculs LCAO-MO des densites de spin d e la fonction d'onde d'un electron des deux especes donnent une bonne correlation entre les couplages hyperfins calcules et observes pour les valeurs des parametres Pc,/Pcc = 1.8,6a = 1.4 permettant ainsi une identification nette des protons aromatiques. E n considerant la dependance angulaire des couplages hyperfins du proton benzylique du cycle A, il est possible de distinguer entre les deux conformations demi-chaise possibles pour la semiquinone de la daunorubicine. On considere, sans I'avoir prouve, que la conformation privilegiee de I'intermediaire est celle dans laquelle les fonctions oxygenees 7 et 9 sont equatoriales et le groupe acetyle en C-9 est axial.[Traduit par le journal]

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Cardiac Toxicity of Daunorubicin

Cited by 171 publications

References 7 publications

Effects of caffeic acid on doxorubicin induced cardiotoxicity in rats

Effects of caffeic acid on doxorubicin induced cardiotoxicity in rats

Adolescent survivor of childhood Acute Myeloid Leukaemia undertakes pregnancy with a severe anthracycline induced cardiomyopathy and risk taking behaviours

Electron paramagnetic resonance characterization and conformation of daunorubicin semiquinone intermediate implicated in anthracycline metabolism, cardiotoxicity, and anticancer action

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