Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 325
Filtrar
1.
Life Sci ; 241: 117173, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843530

RESUMO

PURPOSE: Doxorubicin, as an effective chemotherapeutic drug, is commonly used for combating various solid and hematological tumors. However, doxorubicin-induced cardiotoxicity is considered as a serious adverse effect, and it limits the clinical use of this chemotherapeutic drug. The use of melatonin can lead to a decrease in the cardiotoxic effect induced by doxorubicin. The aim of this review was to evaluate the potential role of melatonin in the prevention of doxorubicin-induced cardiotoxicity. METHODS: This review was conducted by a full systematic search strategy based on PRISMA guidelines for the identification of relevant literature in the electronic databases of PubMed, Web of Science, Embase, and Scopus up to January 2019 using search terms in the titles and abstracts. 286 articles were screened in accordance with our inclusion and exclusion criteria. Finally, 28 articles were selected in this systematic review. RESULTS: The findings demonstrated that doxorubicin-treated groups had increased mortality, decreased body weight and heart weight, and increased ascites compared to the control groups; the co-administration of melatonin revealed an opposite pattern compared to the doxorubicin-treated groups. Also, this chemotherapeutic agent can lead to biochemical and histopathological changes; as for most of the cases, these alterations were reversed near to normal levels (control groups) by melatonin co-administration. Melatonin exerts these protection effects through mechanisms of anti-oxidant, anti-apoptosis, anti-inflammatory, and mitochondrial function. CONCLUSION: The results of this systematic review indicated that co-administration of melatonin ameliorates the doxorubicin-induced cardiotoxicity.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Melatonina/uso terapêutico , Neoplasias/tratamento farmacológico , Cardiotoxicidade/etiologia , Humanos , Neoplasias/patologia , Prognóstico
2.
BMC Complement Altern Med ; 19(1): 317, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744501

RESUMO

BACKGROUND: Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators. METHODS: Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection. RESULTS: A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement. CONCLUSIONS: SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.


Assuntos
Antineoplásicos/toxicidade , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Medicamentos de Ervas Chinesas/administração & dosagem , Mediadores da Inflamação/metabolismo , Animais , Cardiotoxicidade/etiologia , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Coração/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ophiopogon/química , Panax/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
Anticancer Res ; 39(10): 5703-5707, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570470

RESUMO

BACKGROUND/AIM: Anthracyclines, such as doxorubicin, though widely used in anticancer therapy, they are associated with cardiotoxic side-effects. The aim of this trial was to investigate long-term follow-up cardiotoxicity findings in patients treated with doxorubicin and concomitant metoprolol or enalapril 10 years earlier. PATIENTS AND METHODS: Overall, 147 patients were randomized into the treatment arms. A total of 125 patients treated with doxorubicin without evidence of heart disease at the start of chemotherapy were analyzed. They were followed-up for up to 10 years after treatment start. RESULTS AND CONCLUSION: A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Enalapril/uso terapêutico , Linfoma/tratamento farmacológico , Metoprolol/uso terapêutico , Adolescente , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/etiologia , Doxorrubicina/uso terapêutico , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos
4.
Heart Fail Clin ; 15(4): 487-495, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472884

RESUMO

As cancer therapies improve, the population of survivors of cancer has increased, and the long-term effects of cancer treatments have become more apparent. Cardiotoxicity is a well-established adverse effect of many antineoplastic agents. Hypertension is common in survivors of cancer, can be caused or worsened by certain agents, and has been shown to increase the risk of other cardiovascular diseases including heart failure. Pretreatment risk assessment and careful monitoring of blood pressure during therapy is essential. Aggressive management of preexisting or incident hypertension in survivors of cancer is paramount to decrease the risk of heart failure and other cardiovascular diseases in these patients.


Assuntos
Antineoplásicos , Cardiotoxicidade , Insuficiência Cardíaca , Hipertensão , Neoplasias/terapia , Risco Ajustado/métodos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/prevenção & controle , Monitoramento de Medicamentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia
5.
Am J Chin Med ; 47(5): 1075-1097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311298

RESUMO

Pirarubicin (THP) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. Unfortunately, the clinical effectiveness of THP is limited by its dose-related cardiotoxicity. Apocynum leaf extract is an extract of the dried leaves of Apocynum venetum L. (a member of the Apocynaceae family, AVLE) that has many positive effects on the cardiovascular system and is widely consumed as tea in China. In this study we established a cardiactoxicity rat model, which showed that pretreatment with AVLE attenuated THP-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. AVLE also significantly reduced serum levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (CTnT), and lactate dehydrogenase (LDH); and increased serum superoxide dismutase (SOD) levels. Treatment with AVLE or dexrazoxane (DZR) resulted in an increase Cytochrome C (cytc) in the mitochondria and reduced Cytc and cleaved-caspase-3 levels (p<0.05) in cytoplasm. We also found that AVLE significantly reduced voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD) mRNA expression (p<0.05). Furthermore, AVLE appeared to exert therapeutic effects in a dose-dependent manner. Our study suggests the anti-oxidant and anti-apoptotic properties of AVLE may be responsible for the observed cardioprotective effects.


Assuntos
Antioxidantes/administração & dosagem , Apocynum/química , Cardiotoxicidade/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Cardiotoxicidade/fisiopatologia , Creatina Quinase/genética , Creatina Quinase/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Humanos , Masculino , Malondialdeído/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Folhas de Planta/química , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Troponina/genética , Troponina/metabolismo
6.
Life Sci ; 232: 116526, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170418

RESUMO

Tumors and heart disease are two of the leading causes of human death. With the development of anti-cancer therapy, the survival rate of cancer patients has been significantly improved. But at the same time, the incidence of cardiovascular adverse events caused by cancer treatment has also been considerably increased, such as arrhythmia, left ventricular (LV) systolic and diastolic dysfunction, and even heart failure (HF), etc., which seriously affects the quality of life of cancer patients. More importantly, the occurrence of adverse events may lead to the adjustment or the cessation of anti-cancer treatment, which affects the survival rate of patients. Understanding the mechanism of cardiotoxicity (CTX) induced by antineoplastic drugs is the basis of adequate protection of the heart without impairing the efficacy of antineoplastic therapy. Based on current research, a large amount of evidence has shown that oxidative stress (OS) plays an essential role in CTX induced by antineoplastic drugs and participates in its toxic reaction directly and indirectly. Here, we will review the mechanism of action of OS in cardiac toxicity of antineoplastic drugs, to provide new ideas for researchers, and provide further guidance for clinical prevention and treatment of cardiac toxicity of anti-tumor drugs in the future.


Assuntos
Antineoplásicos/metabolismo , Cardiotoxicidade/prevenção & controle , Estresse Oxidativo/fisiologia , Antineoplásicos/efeitos adversos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Cardiotoxicidade/metabolismo , Coração/fisiopatologia , Cardiopatias/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Qualidade de Vida
7.
Pediatr Blood Cancer ; 66(9): e27868, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31148382

RESUMO

BACKGROUND: Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. PROCEDURE: Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. RESULTS: The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. CONCLUSIONS: Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antraciclinas , Sobreviventes de Câncer , Cardiomiopatias , Cardiotoxicidade , Cuidadores , Ecocardiografia , Eletrocardiografia , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Adulto , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatias/prevenção & controle , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Criança , Técnica Delfos , Feminino , Humanos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle
8.
Rev. cuba. pediatr ; 91(2): e735, abr.-jun. 2019.
Artigo em Espanhol | LILACS | ID: biblio-1042940

RESUMO

El reconocimiento inicial de la disfunción cardíaca ocasionada por estrategias terapéuticas aplicadas contra el cáncer fue realizado en la sexta década del siglo xx. La Cardiooncología es una nueva disciplina horizontal dirigida a la identificación de los pacientes en riesgo elevado para el desarrollo de toxicidad cardíaca. El eficaz desempeño inherente a la Cardiooncología pediátrica radica en la adecuada selección del medio diagnóstico capaz de identificar y evaluar los indicios de cardiotoxicidad mediante la detección de cambios precoces en la funcionalidad del miocardio tras la aplicación de terapias antitumorales y, sobre todo, la predicción a largo plazo de estos eventos en niños sobrevivientes de cáncer. La cardiotoxicidad secundaria a la terapéutica aplicada sobre estos pacientes es un problema de salud latente en nuestro país que precisa la adopción de medidas organizativas concebidas para su enfrentamiento. Se persigue contribuir a la estructuración de la atención integral correspondiente al niño con cáncer y afectado por cardiotoxicidad en Cuba(AU)


The initial recognition of cardiac dysfunction caused by therapeutic strategies applied against cancer was performed in the sixth decade of the twentieth century. Cardio-Oncology is a new horizontal discipline aimed at the identification of patients at high risk for the development of cardiac toxicity. The effective performance inherent in Pediatric cardio-oncology lies in the appropriate selection of the diagnostic mean which can be capable of identifying and evaluating the indications of heart toxicity by detecting early changes in myocardial functionality after the application of anti-tumour therapies and, above all, the long-term prediction of these events in children survivors of cancer. Cardiac toxicity secondary to the therapies applied on these patients is a latent health problem in our country that requires the adoption of organisational measures conceived for their confrontation. It is pursued to contribute to the structuring of the comprehensive care corresponding to children with cancer and affected by cardiotoxicity in Cuba(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Doenças Cardiovasculares/complicações , Radioterapia (Especialidade)/métodos , Cardiotoxicidade/complicações , Cardiotoxicidade/prevenção & controle , Antineoplásicos/efeitos adversos
9.
Expert Opin Drug Saf ; 18(6): 485-496, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062991

RESUMO

INTRODUCTION: The angiogenesis mechanism is considered a crucial point in neoplastic development. A growing number of multi-targeted tyrosine kinase inhibitors (TKI) has been developed and approved for cancer treatment during the last few years. Cardiac side effects still remain an issue to manage nowadays. These drugs mechanisms and toxicities have already been discussed, hence the authors will report updates on these already available drugs. AREAS COVERED: This manuscript provides an updated review on the new mechanisms involved in angiogenesis and cardiotoxicity that are TKI-related. Here is reported an overview of the already available and the most recent TKIs under investigation in the oncology field. A literature review has been performed, focusing on the most relevant phase II and phase III trial results. EXPERT OPINION: TKIs represent a new and important resource in the oncology field. Since the use and the number of VEGFR-TKI is constantly increasing, a specific focus on cardiotoxicity development and management appears as justified. Oncologists must record cardiovascular risk factors at baseline in order to stratify patients' risk before undergoing TKI-VEGFRs. A collaboration between oncologists and cardio-oncologists is strongly recommended to earlier manage cardiovascular events (i.e. arterial hypertension) that could interfere with oncological results.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Inibidores da Angiogênese/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Cardiotoxicidade/prevenção & controle , Comportamento Cooperativo , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
10.
Life Sci ; 227: 94-100, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004659

RESUMO

AIMS: Improvements in cancer treatment have significantly extended the lifespan of patients. However, due to the adverse effects of cancer treatment, cancer survivors are at increased risk of cardiovascular complications. Doxorubicin is a widely used spectrum antitumor drug, but the life-threatening side-effect of cardiotoxicity limits its clinical application. Ammonium chloride (NH4Cl), as a heteropolar compound with pH value regulation, can cause intracellular alkalization and metabolic acidosis thus effecting enzymatic activity and influencing the process of biological system. The underlying effect of NH4CL in DOX-induced cardiomyocyte apoptosis and hypertrophy in mice has never been reported before. MAIN METHODS: This study we used DOX to induce cardiac remodeling and dysfunction in mice. Myocardial histology was performed using HE staining. Myocardial cell size was measured by wheat germ agglutinin (WGA) staining. Echocardiographic evaluation of cardiac function, qPCR detection of the mRNA expression of cardiac hypertrophy and inflammation markers. Apoptosis was detected by TUNEL method. Transmission electron microscopy (TEM) was used to detect autophagy. KEY FINDINGS: We found that NH4CL effectively improved DOX-induced cardiomyocyte apoptosis and cardiac dysfunction in mice. Our results showed that NH4CL significantly improved DOX-induced contractile dysfunction, inflammation, apoptosis and autophagy in mice. SIGNIFICANCE: Our results indicate that NH4CL is effective in improving DOX-induced cardiac dysfunction and remodeling. It may therefore be a therapeutic entry point to limit doxorubicin-mediated adverse cardiac reactions.


Assuntos
Cloreto de Amônio/farmacologia , Cardiotoxicidade/prevenção & controle , Coração/efeitos dos fármacos , Cloreto de Amônio/metabolismo , Cloreto de Amônio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cardiomiopatias/metabolismo , Modelos Animais de Doenças , Doxorrubicina/efeitos adversos , Cardiopatias/patologia , Hipertrofia/tratamento farmacológico , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Cardiol Rev ; 27(5): 256-259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31008768

RESUMO

Anthracycline (doxorubicin) and trastuzumab treatments for cancer patients have been known to cause cardiotoxicity. The current recommendations for prevention of cardiac events from cancer chemotherapies are largely based on opinion. The American Society of Clinical Oncology recommends active screening and prevention of modifiable cardiovascular risk factors. The risk factors are defined as tobacco use, high blood pressure, high cholesterol, alcohol use, obesity, and physical inactivity. Beta-adrenergic blockers and angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) have been the mainstay of treatment for heart failure patients with reduced left ventricular ejection fraction for many years. This review analyzed the use of beta-adrenergic blockers and ACE inhibitors/ARBs as protection against cardiomyopathy caused by anthracyclines and trastuzumab. Although many more studies are warranted, it was concluded that the addition of a beta-blocker early in the treatment of cancer patients who are undergoing anthracycline or trastuzumab treatment can have beneficial effects in preserving left ventricular ejection fraction and preventing chemotherapy-induced cardiotoxicity. The effects are more apparent in the short term. More studies of the long-term effects are warranted, as are the additive effects of using a beta-blocker and ACE inhibitor/ARB together to prevent chemotherapy-induced cardiotoxicity.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antraciclinas/efeitos adversos , Cardiopatias/prevenção & controle , Trastuzumab/efeitos adversos , Antraciclinas/toxicidade , Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Cardiopatias/induzido quimicamente , Humanos , Trastuzumab/toxicidade
12.
Bratisl Lek Listy ; 120(4): 249-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31023046

RESUMO

AIM: The present study aimed to determine the protective effect of melatonin and agomelatine on DOX-induced cardiotoxicity in rats by electrocardiographic, scintigraphic and biochemical methods. MATERIALS AND METHODS: Forty-nine male Wistar rats were randomly separated into seven groups; control (CON), doxorubicin (DOX), melatonin (MEL), agomelatine (AGO), melatonin+doxorubicin (MEL+DOX), agomelatine+doxorubicin (AGO+DOX) and melatonin+ agomelatine+ doxorubicin (MEL+AGO+DOX) groups. Cardiotoxicity was induced by intraperitoneal (i.p.) injection of DOX (18 mg/kg daily for three days). Rats receiving MEL and AGO treatment in the DOX-induced cardiotoxicity group received MEL and AGO (40 mg/kg/day, i.p., for seven days). They were injected with doxorubicin (18 mg/kg, i.p.) on days 5, 6, and 7. The rats were given MEL and AGO as substance control (40 mg/kg/day, i.p., for 7 days). On day 8 of the experiment, animals were evaluated by means of electrocardiography (ECG) and 99mtechnetium pyrophosphate (99mTc PYP) scintigraphy and their biochemical parameters [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)] were examined. RESULTS: DOX-induced acute cardiotoxicity in rats is characterized by conduction abnormalities in the ECG pattern (including decreased P wave and QRS complex duration, increased QT and RR intervals, and ST-segment elevation), increased serum BUN, CK, and cTnT parameters and increased 99mTc PYP uptake (p < 0.001). Pretreatment with MEL, AGO, or MEL+AGO effectively alleviated DOX-induced ECG abnormalities close to normal (p < 0.001). Moreover, serum biochemical evidence and 99mTc PYP uptake values demonstrated that pretreatment with MEL, AGO, or MEL+AGO has the same protective effect against the abnormalities produced in the heart by DOX (p < 0.001). CONCLUSIONS: MEL and AGO have a potential protective effect on DOX-induced cardiotoxicity. At the same time, this study suggests that 99mTc PYP is a non-invasive method suitable for early determination of DOX-induced cardiotoxicity (Tab. 3, Fig. 5, Ref. 41).


Assuntos
Antibióticos Antineoplásicos , Antioxidantes , Cardiotoxicidade , Doxorrubicina , Melatonina , Acetamidas/farmacologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Eletrocardiografia , Coração/diagnóstico por imagem , Masculino , Melatonina/farmacologia , Miocárdio , Cintilografia , Ratos , Ratos Wistar
13.
Oncology ; 96(5): 223-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943496

RESUMO

Physical activity is known to prevent the occurrence of cancer and decrease the risk of breast cancer. At diagnosis of breast cancer, fewer than half of the patients reach the international recommendation for physical activity. However, breast cancer patients, and particularly HER2+ breast cancer patients, are exposed to treatment-induced cardiotoxicity because of a side effect of 2 molecules used in standard therapy to treat these tumors, i.e., anthracycline and trastuzumab. Cardiotoxicity can sometimes lead to discontinuation of the treatment and even to the development of cardiovascular diseases. Exercise is known to protect the cardiovascular system in the healthy population. Consequently, being physically active during treatment appears to be a way to prevent the negative impact of cancer treatment on the heart in this population. In particular, aerobic exercising could have a protective effect against treatment-induced cardiotoxicity. A supervised physical activity program seems to be the best way for breast cancer patients to be active during treatment. However, there is very little information, and in particular a lack of guidelines, on exercising available to patients. The interventional trials that have been conducted on this topic are very heterogeneous and no standard recommendations have been made available for cancer patients thus far. An effective physical activity program needs to take each patient's barriers and motivations into account in order to encourage the practice of physical activity throughout treatment. To ensure the success of the program, it is essential to facilitate adherence and especially maintain motivation. Further studies are needed to determine what practice guidelines oncologists should give their patients.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Antraciclinas/efeitos adversos , Neoplasias da Mama/psicologia , Exercício/psicologia , Feminino , Humanos , Cooperação do Paciente/psicologia , Guias de Prática Clínica como Assunto , Trastuzumab/efeitos adversos
14.
PLoS One ; 14(4): e0214984, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30947243

RESUMO

Type 2 diabetes (T2D) is characterised by ß-cell damage and hyperglycaemia. The lipophilic drug, probucol, has shown significant ß-cell protective and potential antidiabetic effects, which were enhanced by hydrophilic bile acid incorporation using taurocholic acid and chenodeoxycholic acid. However, probucol has severe cardiotoxicity and a variable absorption profile, which limit its potential applications in T2D. Accordingly, this study aimed to design multiple formulations to optimise probucol oral delivery in T2D and test their effects on probucol absorption and accumulation in the heart. Adult male mice were given a high fat diet (HFD), and a week later, injected with a single dose of alloxan to accelerate T2D development, and once diabetes confirmed, divided into three groups (six to seven mice each). The groups were gavaged a daily dose of probucol powder, probucol microcapsules, or probucol-bile acid microcapsules for three months, and euthanized; and blood, tissues, and feces collected for blood glucose and probucol concentration analyses. Probucol concentrations in plasma were similar among all the groups. Groups given probucol microcapsules and probucol-bile acid microcapsules showed significant reduction in probucol accumulation in the heart compared with the group given probucol powder (p<0.05). Probucol microencapsulation with or without bile acids reduced its accumulation in heart tissues, without changing plasma concentrations, which may be beneficial in reducing its cardiotoxicity and optimise its potential applications in T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Probucol , Administração Oral , Animais , Cápsulas , Cardiotoxicidade/sangue , Cardiotoxicidade/prevenção & controle , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio/metabolismo , Probucol/farmacocinética , Probucol/farmacologia
15.
BMC Pharmacol Toxicol ; 20(1): 18, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023386

RESUMO

BACKGROUND: The effects of ß blockers on the primary prevention of anthracycline-induced cardiotoxicity were controversial. METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of the comparison of ß blockers versus placebo in patients undergoing anthracycline chemotherapy. This meta-analysis was performed by using random-effect models. RESULTS: Nine hundred forty participants from 11 trials were included in this meta-analysis. ß blockers led to a significant reduction in symptomatic heart failure (risk ratio [RR] 0.29, 95% CI 0.10 to 0.85). Compared with placebo, ß blockers were associated with improved left ventricular ejection fraction (mean difference [MD] 4.46, 95% CI 1.77 to 7.15) and s' (MD 0.78, 95% CI 0.01 to 1.55) in parallel with reduced left ventricular diameter (left ventricular end systolic diameter, MD -3.19, 95% CI -6.17 to - 0.21; left ventricular end diastolic diameter, MD -2.28, 95% CI 4.50 to - 0.05). ß blockers also improved strain and strain rate when compared with placebo. There were no significant differences in diastolic function variables between ß blockers and placebo except e' (MD 2.33, 95% CI 0.16 to 4.51). In addition, ß blockers compared with placebo reduced the risk of cardiac troponin I elevation > 0.04 ng/ml (RR 0.60, 95% CI 0.42 to 0.85). There was no marked difference in adverse events (RR 0.94, 95% CI 0.56 to 1.59) between ß blockers and placebo. CONCLUSIONS: In cancer patients with anthracycline therapy, prophylactic ß blockers were associated with reduced risk of heart failure, decreased left ventricular diameter, improved left ventricular systolic function, and alleviative cardiomyocyte injury.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Humanos , Neoplasias/tratamento farmacológico , Prevenção Primária , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
BMC Cancer ; 19(1): 270, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917783

RESUMO

BACKGROUND: Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. METHODS: We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995-2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. RESULTS: Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65-1.85) or any cancer event (HR = 1.12, 95%CI = 0.85-1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44-1.21) or any cancer event (HR = 0.93, 95%CI = 0.70-1.24). CONCLUSIONS: Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.


Assuntos
Anti-Hipertensivos/administração & dosagem , Cardiotoxicidade/prevenção & controle , Neoplasias do Colo/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Recidiva Local de Neoplasia/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Sobreviventes de Câncer , Estudos de Coortes , Neoplasias do Colo/etiologia , Registros Eletrônicos de Saúde , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Segunda Neoplasia Primária/etiologia , Modelos de Riscos Proporcionais
18.
Herz ; 44(2): 175-188, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30847511

RESUMO

Recent advances in the medical oncological treatment options for cancer have led to a clear improvement in the survival rate worldwide; however, many of the recently developed new drugs are directly or indirectly associated with cardiovascular side effects. Cardiovascular diseases are already the most frequent non-cancerous cause of death in tumor patients. Prevention, early detection of these complications, correct management and timely initiation of specific cardiac medical treatment are the key for an improvement of the cardiovascular prognosis. This article provides an overview and comprehensive summary of the possible cardiotoxic side effects of important oncological therapies and offers possible practical strategies with respect to risk stratification, cardiological follow-up care and management approaches for chemotherapy-induced left ventricular dysfunction.


Assuntos
Antineoplásicos , Cardiotoxicidade , Neoplasias , Cardiotoxicidade/prevenção & controle , Detecção Precoce de Câncer , Humanos , Oncologia , Neoplasias/terapia
19.
Biomed Pharmacother ; 113: 108731, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30851549

RESUMO

BACKGROUND: Cisplatin (CP) has been used in wide range for cancer treatment. Although nephrotoxicity of CP was the main complication, cardiotoxicity has been reported. OBJECTIVES: This study investigates the protective role of green tea extract (GTE) and vitamin E (Vit-E) against CP-induced cardiotoxicity, and assesses their impact on CP antitumor efficacy. MATERIALS AND METHODS: Forty-eight male albino Balb/c mice were randomly divided into six groups, 8 per/group (Gp) were included. Gp1 served as control; Gp2 and Gp3 received oral GTE (400 mg/kg) and Vit-E (100 mg/kg) for 30 consecutive days respectively. Gp4 had received CP (7 mg/kg i.p.) once on the 27th day; Gp5 had received GTE (400 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Gp6 had received Vit-E (100 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Blood and tissues samples were harvested for biochemical and histopathological investigations. To evaluate the effect of GTE and Vit-E on the antitumor efficacy of CP, 49 female albino mice were inoculated intraperitoneally by Ehrlich ascetic carcinoma -cells (2 × 106/mouse) then treated with none, corn oil, CP, CP/GTE, CP/Vit-E, GTE or Vit-E. RESULTS: CP injection significantly increased Troponin I, CPK, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, while glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase levels were significantly reduced with disruption of cardiac muscle fibers, loss of striations, absence of intercalated disc, and the nuclei are pyknotic. Treatment with GTE and Vit-E improve the biochemical and histological parameters. Treatment with CP alone led to eradication of the tumor cells from the tumor-bearing mice. However, co-administration of GTE or Vit-E orally with CP did not interfere with its therapeutic effects. CONCLUSION: Treatment with GTE and Vit-E significantly ameliorated the CP cardiotoxicity and improved the myocardial histopathological architecture. GTE and Vit-E may be combined with CP to alleviate cardiotoxicity in cancer chemotherapy without interfering with its antitumor activity.


Assuntos
Cardiotoxicidade/prevenção & controle , Cisplatino/toxicidade , Extratos Vegetais/farmacologia , Chá/química , Vitamina E/farmacologia , Animais , Antineoplásicos/toxicidade , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacologia , Cardiotoxicidade/etiologia , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Superóxido Dismutase/metabolismo , Resultado do Tratamento , Vitamina E/administração & dosagem
20.
Food Chem Toxicol ; 125: 503-519, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30735749

RESUMO

The present investigation has been undertaken to reveal the protective mechanism of polyphenolics extract of whole wheat grains (WWGPE), ferulic acid and apigenin against doxorubicin (Dox)-induced cardio-toxicity. WWGPE, apigenin, and ferulic acid exhibited concentration dependent cyto-protective effect against Dox (1 µM) in rat cardiomyocytes. Dox treatment significantly (p < 0.01) induced oxidative stress in the myocardial cells via excessive ROS production, increase in iNOS expression, NADPH oxidase activation, Nrf-2/HO-1 impairment, and inactivation of cellular redox defense system. In addition, Dox significantly (p < 0.01) activated MAP kinases, NF-κB, and apoptosis in cardiac cells; while, significant (p < 0.01) impairment in PI3K/Akt/mTOR signaling was observed in Dox-treated myocardial cells. On the other hand, WWGPE, apigenin, and ferulic acid significantly (p < 0.05-0.01) attenuated Dox-induced redox stress and oxidative stress-mediated signal transduction in myocardial cells. WWGPE, apigenin, and ferulic acid treatment also could significantly (p < 0.05-0.01) reinstate Dox-mediated changes in blood parameters in rats. Histological assessments were in agreement with the biochemical findings. Results showed that, WWGPE exhibited better cardio-protective effect over ferulic acid and apigenin, which may be due to the synergy between the comprising compounds and better oral bioavailability of dietary antioxidant molecules from whole phenolic extract.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotoxicidade/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apigenina/isolamento & purificação , Apigenina/farmacologia , Cardiotônicos/isolamento & purificação , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/farmacologia , Doxorrubicina , Cardiopatias/induzido quimicamente , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Polifenóis/isolamento & purificação , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Triticum/química , Grãos Integrais/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA