Anthracycline-Induced Cardiotoxicity
Anthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by “redox-cycl...
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| Format: | Article |
| Language: | English |
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Karolinum Press
2000-01-01
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| Series: | Acta Medica |
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| Online Access: | https://actamedica.lfhk.cuni.cz/43/3/0075/ |
| _version_ | 1831521658795458560 |
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| author | Radomír Hrdina Vladimír Geršl Ivona Klimtová Tomáš Šimůnek Jarmila Macháčková Michaela Adamcová |
| author_facet | Radomír Hrdina Vladimír Geršl Ivona Klimtová Tomáš Šimůnek Jarmila Macháčková Michaela Adamcová |
| author_sort | Radomír Hrdina |
| collection | DOAJ |
| description | Anthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by “redox-cycling“ of anthracycline molecule and/or by the formation of anthracycline-ferric ion complexes. The iron catalyzes the hydroxyl radical production via Haber-Weiss reaction. The selective toxicity of ANT against cardiomyocytes results from high accumulation of ANT in cardiac tissue, appreciable production of oxygen radicals by mitochondria and relatively poor antioxidant defense systems. Other additional mechanisms of the anthracycline cardiotoxicity have been proposed - calcium overload, histamine release and impairment in autonomic regulation of heart function. The currently used methods for an early identification of anthracycline cardiotoxicity comprise ECG measurement, biochemical markers, functional measurement and morphologic examination. Among a plenty of studied cardioprotective agents only dexrazoxane (ICRF-187) has been approved for clinical use. Its protective effect likely consists in intracellular chelating of iron. However, in high doses dexrazoxane itself may cause myelotoxicity. This fact encourages investigation of new cardioprotectants with lower toxicity. Orally active iron chelators and flavonoids attract more attention. Modification of dosage schedule and synthesis of new anthracycline analogues may represent alternative approaches to mitigate anthracycline cardiotoxicity while preserving antitumour activity. |
| first_indexed | 2024-12-14T00:11:42Z |
| format | Article |
| id | doaj.art-0e921a2dd83545d4bd2f3fa218f9bc79 |
| institution | Directory Open Access Journal |
| issn | 1211-4286 1805-9694 |
| language | English |
| last_indexed | 2024-12-14T00:11:42Z |
| publishDate | 2000-01-01 |
| publisher | Karolinum Press |
| record_format | Article |
| series | Acta Medica |
| spelling | doaj.art-0e921a2dd83545d4bd2f3fa218f9bc792022-12-21T23:25:43ZengKarolinum PressActa Medica1211-42861805-96942000-01-01433758210.14712/18059694.2019.117Anthracycline-Induced CardiotoxicityRadomír Hrdina0Vladimír Geršl1Ivona Klimtová2Tomáš Šimůnek3Jarmila Macháčková4Michaela Adamcová5Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Hradec Králové, Czech RepublicCharles University in Prague, Faculty of Medicine in Hradec Králové, Department of Pharmacology, Hradec Králové, Czech RepublicCharles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Hradec Králové, Czech RepublicCharles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Hradec Králové, Czech RepublicCharles University in Prague, Faculty of Medicine in Hradec Králové, Department of Pharmacology, Hradec Králové, Czech RepublicCharles University in Prague, Faculty of Medicine in Hradec Králové, Department of Physiology, Hradec Králové, Czech RepublicAnthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by “redox-cycling“ of anthracycline molecule and/or by the formation of anthracycline-ferric ion complexes. The iron catalyzes the hydroxyl radical production via Haber-Weiss reaction. The selective toxicity of ANT against cardiomyocytes results from high accumulation of ANT in cardiac tissue, appreciable production of oxygen radicals by mitochondria and relatively poor antioxidant defense systems. Other additional mechanisms of the anthracycline cardiotoxicity have been proposed - calcium overload, histamine release and impairment in autonomic regulation of heart function. The currently used methods for an early identification of anthracycline cardiotoxicity comprise ECG measurement, biochemical markers, functional measurement and morphologic examination. Among a plenty of studied cardioprotective agents only dexrazoxane (ICRF-187) has been approved for clinical use. Its protective effect likely consists in intracellular chelating of iron. However, in high doses dexrazoxane itself may cause myelotoxicity. This fact encourages investigation of new cardioprotectants with lower toxicity. Orally active iron chelators and flavonoids attract more attention. Modification of dosage schedule and synthesis of new anthracycline analogues may represent alternative approaches to mitigate anthracycline cardiotoxicity while preserving antitumour activity.https://actamedica.lfhk.cuni.cz/43/3/0075/AnthracyclinesCardioprotectionCardiotoxicityDaunorubicinDexrazoxaneDoxorubicin |
| spellingShingle | Radomír Hrdina Vladimír Geršl Ivona Klimtová Tomáš Šimůnek Jarmila Macháčková Michaela Adamcová Anthracycline-Induced Cardiotoxicity Acta Medica Anthracyclines Cardioprotection Cardiotoxicity Daunorubicin Dexrazoxane Doxorubicin |
| title | Anthracycline-Induced Cardiotoxicity |
| title_full | Anthracycline-Induced Cardiotoxicity |
| title_fullStr | Anthracycline-Induced Cardiotoxicity |
| title_full_unstemmed | Anthracycline-Induced Cardiotoxicity |
| title_short | Anthracycline-Induced Cardiotoxicity |
| title_sort | anthracycline induced cardiotoxicity |
| topic | Anthracyclines Cardioprotection Cardiotoxicity Daunorubicin Dexrazoxane Doxorubicin |
| url | https://actamedica.lfhk.cuni.cz/43/3/0075/ |
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