Doxorubicin is a widely used chemotherapy drug, but its application is associated with cardiotoxicity. Dantrolene attenuates cardiotoxicity of doxorubicin. Doxorubicin hydrochloride for injection, usp doxorubicin. In conclusion, the protective role of quercetin against doxorubicin cardiotoxicity could be ascribed mainly to its antioxidant activity. Pdf we investigated the effects of artemisinin on doxorubicin dox induced heart and liver pathology in rats. Potentiation of doxorubicin cardiotoxicity by iron loading. Doxorubicin induces cardiotoxicity through upregulation of.
Anthracycline cardiotoxicity and radiationinduced heart disease rihd are now classified as sensitivity and toxic reactions under the broad category of. Cardiac analysis of autologous transplantation of cocultured skeletal myoblasts and mesenchymal cells in a rat model doxorubicin induced cardiotoxicity. One of that is cardiotoxicity by inducing the expression of nitric oxide synthase which may release. Cardiotoxicity of doxorubicin and other anthracycline. Doxorubicin is a potent anticancer drug with cardiotoxicity hampering its use. Doxorubicin dox is an important drug in modern therapy for breast cancer, softtissue sarcomas, acute leukemia, hodgkins and nonhodgkins lymphoma, and many childhood cancers. Department of experimental oncology, national cancer research center. The incidence of acute cardiotoxicity is approximately 11%. Pdf insights into mechanisms of doxorubicin cardiotoxicity. Risk factors for developing doxorubicin induced cardiotoxicity include. Another influential factor in chemotherapyinduced cardiotoxicity is the peak serum concentration reached during administration.
Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus hivassociated kaposi sarcoma ks. Doxorubicin dox is an anthracycline antitumor antibiotic used to treat many malignancies in dogs and people, including lymphoma, osteosarcoma, soft tissue sarcoma. Yeh, mdy abstract anthracycline compounds are major culprits in chemotherapy. Cardiac function should be assessed at baseline and continue during treatment. Valdiviezo, navneet narula, jagat narula, diwakar jain the role of. Doxorubicin is one of the most active drugs in oncology, with cardiotoxicity as a serious side effect of its application. Cardiac toxicity with doxorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present. Pdf cardiac analysis of autologous transplantation of. Cardioprotective effects of sitagliptin against doxorubicininduced. Cardioprotective effect of kelor moringa oleifera leaf.
Congestive heart failure in patients treated with doxorubicin. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a. Prevention of anthracyclineinduced cardiotoxicity challenges and opportunities pimprapa vejpongsa, md, edward t. The complex and not completely understood pathogenesis of. Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via. Doxorubicin showed better activity than daunorubicin against mouse tumors, and especially solid tumors. Potentiation of doxorubicin cardiotoxicity by iron loading in a rodent model gurusher s. In doxorubicin cardiomyopathy, there are areas of patchy myocardial.
Free radical generation and mitochondrial dysfunction are thought to contribute to. Sitagliptin protects against doxorubicin cardiotoxicity. The aim of this study was to investigate dexrazoxane and amifostine. Early evidence of cardiotoxicity and tumor response in. Doxorubicin hydrochloride injection, usp, is a sterile parenteral, isotonic solution. Cardiomyopathy induced by doxorubicin dox is considered an extremely serious adverse. The mechanisms of doxorubicininduced cardiotoxicity remain incompletely understood. Congestive heart failure in patients treated with doxorubicin a retrospective analysis of three trials sandra m. Neuropeptide y npy is the most abundant neuropeptide in the heart and a cotransmitter of the. Doxorubicininduced cardiotoxicity is suppressed by. Thrombopoietin protects against in vitro and in vivo.
The histology slides were examined by light microscopy olympus cx31 to assess histopathological changes. Doxorubicin hydrochloride for injection, usp, is a sterile redorange lyophilized powder. Background doxorubicin dox is an important antineoplastic agent. Cardiomyocytespecific disruption of cathepsin k protects against doxorubicininduced cardiotoxicity. Doxorubicin causes cumulative cardiac toxicity, which limits the total life. Despite welldocumented cardiotoxic effects, doxorubicin remains a. Doxorubicin, oxidative stress, free radicals, cardiotoxicity. The cytotoxic effect of doxorubicin on malignant cells and its toxic effects on various organs. Doxorubicin cardiotoxicity has posed a formidable challenge in the fields of oncology, cardiology, pharmacology, biochemistry, pathology, and molecular biology whereas development of a. The extent of histopathology was scored on a scale of.
Doxorubicin dox is an anthracycline antibiotic commonly used for treatment of various malignancies. The role of iron toward doxorubicin dox cardiotoxicity was studied using a rodent model of dietary carbonyl iron loading. The anticancer drug doxorubicin dox also referred to as adriamycin is highly effective in the treatment of a broad range of cancers. Quercetininduced cardioprotection against doxorubicin. Doxorubicin dox is an anticancer drug in the anthracycline class used to treat a variety of malignances including breast tumors 1. These results agreed well with findings on dox cardiotoxicity examined using histopathology and immunohistochemistry techniques panjrath. The anthracycline doxorubicin dox is widely used in chemotherapy due to its efficacy in fighting a wide range of cancers such as carcinomas, sarcomas and hematological cancers. Doxorubicin, epirubicin, cardiotoxicity, malignancy, cancer, cardiomyocytes.
Glutamine regulation of doxorubicin accumulation in hearts. Sinapic acid ameliorates oxidative stress, inflammation. Purpose doxorubicin dox, an evective antineoplastic agent is known for its cardiotoxicity attributed mainly to free radical formation. Maximum anthracycline doses guidance london cancer. The manifestations are usually chest pain due to myopericarditis andor palpitations due to sinus tachycardia, paroxysmal nonsustained supraventricular tachycardia and premature atrial and ventricular. The usage of doxorubicin dox as an anticancer drug in cancer patient may cause several side effects. Oxidative stress is a major cause of doxorubicininduced cardiotoxicity. Pediatric patients are at increased risk for developing delayed cardiotoxicity. Kaya, effect of melatonin on the cardiotoxicity of doxorubicin, histology and histopathology. The ability to decrease ros levels and dna damage and maintain cardiac. Pdf on nov 14, 2018, danubia silva dos santos and others published doxorubicininduced cardiotoxicity. However, in a large metaanalysis by van dalen et al. Pdf doxorubicin dox is an anthracycline antibiotic, which is currently one. It also showed a higher therapeutic index, yet the cardiotoxicity remained.
This study evaluates early evidence of cardiotoxicity in patients. Effects of dexrazoxane and amifostine on evolution of. Pathology of radiation and anthracycline cardiotoxicity. This has led important new uses for the mechanism of doxorubicin induced cardiotoxicity and novel avenues of investigation to determine better pharmacotherapies and interventions for the. The incidence of acute cardiotoxicity is approximately 11% 3,4. Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. Cancer has continually been the leading cause of death worldwide for decades. Cardiotoxicity from trastuzumab is largely reversible and therefore characterized as causing type ii chemotherapyrelated cardiac dysfunction. Cardioprotection of dexrazoxane dzr against doxorubicin doxinduced cardiotoxicity is contentious and the indicator is controversial. Cardiomyocytespecific disruption of cathepsin k protects. The cardiotoxicity of doxorubicin is becoming an interdisciplinary point of interest given a growing population of cancer survivors.
A pairwise comparative metabolomics approach was used to. Doxorubicin cardiotoxicity can be acute, occurring during and within 23 days of its administration. Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. Doxorubicin doxo is a common drug of class anthracycline and is a hydroxyl derivative of daunorubicin. Protective effects of dexrazoxane against doxorubicin. The interplay between genetic background and sexual. Comparison of cardiac troponin i and t, including the. Preliminary data indicated that oral glutamine gln reduced cardiac. Secondary acute myelogenous leukemia aml or myelodysplastic syndrome mds have been reported in patients treated. The effects of neuropeptide y overexpression on the mouse. A single published study of chronic cardiotoxicity in doxorubicintreated rats made a direct comparison of ctni and ctnt and showed that ctnt concentration correlated most closely with the. Incidence and risk factors associated with development of. Doxorubicin dox is a very effective anticancer medication that is commonly used to treat hematological malignancies and solid tumors.
Thus, scientists have actively devoted themselves to studying cancer therapeutics. Histological evidence for the cardiac safety of highdose. These results were supported by the histopathological results. The mechanisms of doxorubicin induced cardiotoxicity remain incompletely understood. Quercetin attenuates doxorubicin cardiotoxicity by. Maximum anthracycline doses guidance the following recommendations are for adult patients and are based on information from various sources, including the drug manufacturers and the references.
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