Doxorubicin-Induced Cardiomyopathy

Takemura, Genzou; Fujiwara, Hisayoshi

doi:10.1016/j.pcad.2006.10.002

Cited by 695 publications

(305 citation statements)

References 149 publications

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“…Jednym ze sposobów walki z chorobami nowotworowymi jest chemioterapia, którą zalicza się do terapii systemowych. Wśród najczęściej stosowanych leków przeciwnowotworowych znajdują się antybiotyki antracyklinowe, które od ponad 40 lat są stosowane w leczeniu różnych nowotworów [19].…”

Section: Właściwości Antyoksydacyjne Fulerenoli a Chemioterapiaunclassified

Fullerenols in therapy and diagnosis of cancer

Lichota¹,

Krokosz²

2016

Med Pr

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StreszczenieDo głównych przyczyn zgonów w Polsce zalicza się nowotwory złośliwe. Jednym z celów współczesnych badań biomedycznych jest zmaksymalizowanie efektów działania stosowanych strategii leczniczych. Podejmowane działania doskonalące środki terapeutyczne są ukierunkowane na ograniczenie działań niepożądanych terapii przeciwnowotworowych. Innym kierunkiem badań jest poszukiwanie substancji ochronnych, które zmniejszą toksyczność leków wobec komórek prawidłowych. Nanotechnologia umożliwia projektowanie wyspecjalizowanych nanocząstek, dzięki którym możliwe będzie skuteczniejsze leczenie chorób nowotworowych, a także ich bezpieczne diagnozowanie. Nanomateriały na bazie węgla (fulereny i ich pochodne, grafen, nanorurki wę-glowe, nanodiamenty) stanowią obszerną grupę nanocząstek, które mają potencjalne zastosowania biomedyczne zarówno w terapii, jak i diagnostyce. Celem niniejszej pracy jest omówienie właściwości biologicznych fulerenoli w kontekście ich wykorzystania w różnych strategiach terapii przeciwnowotworowych. W pracy omówiono także możliwości jednoczesnego wykorzystania nanocząstek w terapii i diagnostyce, czyli teranostyce. Obecny stan wiedzy wskazuje, że fulereny i ich hydrofilowe pochodne, w szczególności fulerenole, wykazują niską toksyczność lub jej brak. Poprzez swoje właściwości antyoksydacyjne, a także regulujące ekspresję genów zaangażowanych w proces apoptozy i angiogenezy oraz stymulowanie odpowiedzi immunologicznej, mogą przyczyniać się do hamowania rozrostu guza i ochrony komórek prawidłowych. Gadolin zamknięty w klatce fulerenu jest mniej toksyczny jako środek cieniujący w rezonansie magnetycznym i może jednocześnie hamować rozwój nowotworu, co jest obiecującym wynikiem dla teranostyki. Med. Pr. 2016;67(6):817-831 Słowa kluczowe: nanotechnologia, fuleren, fulerenol, terapia przeciwnowotworowa, obrazowanie molekularne, teranostyka AbstractMalignant tumors are one of the main causes of death in Poland. One of the objectives of contemporary biomedical research is to maximize the effects of therapeutic strategies. The actions undertaken to improve therapeutic agents are aimed at reducing the side effects of cancer treatments. Another direction of investigations is the search for protective substances that reduce the toxicity of the drug to normal cells. Carbon-based nanomaterials (fullerenes and their derivatives, graphene, carbon nanotubes, nanodiamonds) are a broad class of nanoparticles that have potential biomedical applications in both therapy and diagnostics. The aim of this paper is to review biological properties of fullerenols in the context of their use in various strategies of cancer treatments. The authors also discuss the possibility of simultaneous use of nanoparticles in therapy and diagnosis, that is, in theranostics. Current knowledge indicates that fullerenes and their hydrophilic derivatives, especially fullerenols, show low or no toxicity. They may contribute to the inhibition of tumor growth and protection of normal cells through their antioxidant properties, as well as t...

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Section: Właściwości Antyoksydacyjne Fulerenoli a Chemioterapiaunclassified

Fullerenols in therapy and diagnosis of cancer

Lichota¹,

Krokosz²

2016

Med Pr

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“…Due to the appearance of adverse cardiac events in a dose-dependent manner, 500 mg/m 2 has been established as the maximum safe dose of DOX [16]. Apart from determining the concentration limits to ensure the safest possible use of DOX, a variety of prevention and management measures are followed for cancer patients undertaking ANT-based regimes [16,17]. Early diagnosis of DOX-induced cardiotoxicity is essential, since once patients develop advanced-stage HF, their prognosis is not favorable.…”

Section: Anthracycline-based Chemotherapy: Doxorubicinmentioning

confidence: 99%

“…This important fact suggests that the mechanisms underlying DOX tumour and cardiac cytotoxicity are likely to be different. The existence of differential mechanisms of cell death induction in cancer cells and in the myocardium would facilitate the development of less cardiotoxic ANTs [17]. …”

Section: Mechanisms Of Dox-induced Cardiotoxicity: Reactive Oxygen Spmentioning

confidence: 99%

Breast Cancer Treatment and Adverse Cardiac Events: What Are the Molecular Mechanisms?

et al. 2012

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Cardiotoxicity associated with breast cancer treatment is an important concern in the oncology clinic. Different types of anti-cancer therapies have recorded high rates of cardiac dysfunction in treated patients. Cardiac dysfunction linked to anthracyclines – one of the most common conventional chemotherapies – has extensively been described and several mechanisms have been proposed, although their mode of action is not fully understood even in cancer cells. The mediation of cardiac damage by reactive oxygen species stress is a recent hypothesis that has attracted a lot of interest, since it might explain the tissue-specific toxic effects of anthracyclines in the heart. Regarding molecular targeted tyrosine kinase inhibitors used in patients with human epidermal growth factor receptor type 2+ tumours (e.g., trastuzumab, lapatinib), it is the blockage of survival pathways required for a normal heart development and function that seems to lead to cardiac pathology. Both types of breast cancer treatment appear to trigger cardiotoxicity synergically, being patients under adjuvant therapy closely monitored. Given the complex nature of heart failure and of the pathways altered by anti-cancer drugs, global gene expression regulation is key in the heart disease process. MicroRNAs have been demonstrated to be small molecules with big roles as essential gene expression modulators. The great potential of microRNAs as biomarkers in the cardio-oncology field needs to be further explored before new microRNA-based diagnostic and therapeutic tools can be developed.

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“…Numerous studies have focused on the mechanism of anthracycline cardiotoxicity. Studies have suggested that the mechanism of Doxorubicin-induced cardiotoxicity involve the formation of free oxygen radicals, expression of nitric oxide, damage of myocardial mitochondria and alterations of molecular signaling [9] [10]. Amongst these diverse hypotheses, free oxygen radicals from Adriamycin semiquinones are generally believed to play a major role in the pathogenesis of Doxorubicin-induced heart failure [9]- [11].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Grape Seed Extract on Cardiotoxicity Induced by Doxorubicin Drug in Male Rats

Al-Sowayan¹,

Mahmoud²

2014

ABB

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Objective: This work was designed to determine the productive effect of grape seed proanthocynadine extract (GSPE) and Vitamin E against Doxorubicin (DOX) induced myocardial toxicity in 50 male. Wister rates were divided in five groups. The 1 st group was untreated and served as a control. The 2 nd group was treated with DOX only, the 3 rd group was pretreated with GSPE, the 4 th group was pretreated with Vitamin E, and the 5 th group was pretreated with GSPE and Vitamin E. DOX was administered by single i.p (Intraperitonial) injection of 15 mg/kg/body weight to induce cardio toxicity and Vitamin E was administered at a dose of 400 IU/kg/bodyweight/day, p.o (per oral) for 10 days prior to DOX administration [1]. GSPE was given at a dose of 150 mg/kg/bodyweight/ day, p.o (per oral) for 10 days before treatment with DOX. After 2 weeks experimental period, blood samples and heart tissues were taken from all groups. The general observations, mortality, histopathology, biomarker enzymes like Lactate Dehydrogenase (LDH), Creatine Phosphokinase (CPK), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Antioxidants such as Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA) were monitored after 2 weeks of the last dose. Results: Administration of DOX caused cardiomyopathy associated with an antioxidant deficiency. Pretreatment with GSPE and Vitamin E significantly (P < 0.01) protected the myocardium from the toxic effects of DOX by reducing the elevated level of biomarkers and diagnostic enzymes like LDH, CPK, AST, and ALT to normal levels. GSPE and Vitamin E increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Conclusion: These results suggest a cardioprotective effect of GSPE and Vitamin E due to its antioxidant properties.

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Doxorubicin-Induced Cardiomyopathy

Cited by 695 publications

References 149 publications

Fullerenols in therapy and diagnosis of cancer

Fullerenols in therapy and diagnosis of cancer

Breast Cancer Treatment and Adverse Cardiac Events: What Are the Molecular Mechanisms?

The Protective Effect of Grape Seed Extract on Cardiotoxicity Induced by Doxorubicin Drug in Male Rats

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