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2.
Int. j. morphol ; 41(1): 231-236, feb. 2023. ilus, tab, graf
文章 在 英语 | LILACS | ID: biblio-1430516

摘要

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.


La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.


Subject(s)
Animals , Rats , Carotenoids/administration & dosage , Doxorubicin/toxicity , Cucurbita/chemistry , Cardiotoxicity/prevention & control , Cardiotonic Agents , Lipid Peroxidation , Catalase , Rats, Wistar , Oxidative Stress/drug effects , Glutathione Peroxidase , Glutathione Transferase , Antibiotics, Antineoplastic/toxicity , Neoplasms/drug therapy , Antioxidants
3.
文章 在 中文 | WPRIM | ID: wpr-981482

摘要

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.


Subject(s)
Humans , Paclitaxel/pharmacology , Liposomes/chemistry , Ginsenosides/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Cardiotoxicity/drug therapy , Cell Line, Tumor
4.
Rev. urug. cardiol ; 38(1): e201, 2023. ilus, graf, tab
文章 在 西班牙语 | BNUY, UY-BNMED, LILACS | ID: biblio-1442149

摘要

Introducción: las enfermedades cardiovasculares (CV) son la primera causa de muerte en quienes sobreviven al cáncer. Aunque el trasplante de progenitores hematopoyéticos (TPH) se asocia con grados variables de cardiotoxicidad, estas complicaciones han sido escasamente caracterizadas. Objetivo: analizar el perfil de liberación de biomarcadores miocárdicos como potenciales indicadores subclínicos de cardiotoxicidad en pacientes sometidos a TPH. Material y método: estudio descriptivo, analítico, prospectivo transversal y unicéntrico, reclutando pacientes derivados a la policlínica de cardio-oncología, con indicación de TPH en octubre de 2018-marzo de 2020. Se realizaron controles clínicos, ECG, bioquímicos (troponina I TnI y péptido natriurético del tipo BBNP) e imagenológicos según algoritmo de seguimiento. Las variables discretas se presentan como n (%) y las continuas mediante media ± DE o mediana RIQ. Los valores evolutivos de biomarcadores séricos se compararon mediante test de Friedman. La fracciónde eyección del VI (FEVI) basal se comparó con la de los 3 meses del TPH mediante test de Wilcoxon. Resultados: se incluyeron 19 pacientes, 37% mujeres, de 43,8 ± 15,7 años. No se detectaron modificaciones significativas de la FEVI en los controles evolutivos. En ningún caso se observó aumento de la TnI. Los valores de BNP aumentaron en 6 pacientes (32%), con diferencias significativas al mes postrasplante (basal: 13,6 1;6,1-30,9 vs. primer mes: 38,9 16,3-120,0 pg/ml, p = 0,036); con una mayor elevación en aquellos pacientes que recibieron antimetabolitos vs. otros fármacos (basal: 13,6 1;6,1-30,9 vs. al primer mes: 67,0 ;21,3-174,9 pg/ml, p = 0,039). El aumento de BNP no se asoció con el riesgo CV. Conclusión: la liberación de BNP posterior al TPH es un fenómeno frecuente (32% de los pacientes), alcanza un máximo al mes, independientemente de la FEVI. El subgrupo de pacientes que recibió antimetabolitos presentó una mayor liberación precoz de BNP.


Introduction: cardiovascular (CV) diseases are the leading cause of death in those who survive cancer. Although hematopoietic stem cell transplantation (HSCT) is associated with diverse grades of cardiotoxicity, these complications have been poorly characterized. Objective: to analyze the release profile of myocardial biomarkers as a potential subclinical marker of cardiotoxicity in patients undergoing HSCT. Material and method: descriptive, analytical, prospective, cross-sectional, single-center study, recruiting patients referred to the cardio-oncology polyclinic, with indication for HSCT in October 2018-March 2020. Clinical, ECG, biochemical and imaging controls were performed according to the algorithm of follow-up. The evolutionary values of serum biomarkers were compared using the Friedman test. Baseline LVEF was compared with that of 3 months after HSCT using the Wilcoxon test. Results: 19 patients were included, 37% women, aged 43.8 ± 15.7 years. No changes in LVEF were detected. In no case was an increase in TnI observed. BNP values increased in 6 patients (32%), with significant differences one month after transplantation (baseline: 13.6 ;6.1-30.9 vs. first month: 38.9 ;16.3-120.0, p = 0.036), detecting a greater elevation in those patients who received antimetabolites vs. other rugs (baseline: 13.6 ;6.1-30.9 vs. at the first month: 67.0 21.3-174.0, p = 0.039). The increase in BNP was not associated with CV risk. Conclusion: BNP release after HSCT is frequent (32% of our patients), reaching a maximum at one month, regardless of LVEF. The subgroup of patients who received antimetabolites had a greater early release of BNP.


Introdução: as doenças cardiovasculares (CV) são a principal causa de morte em pessoas que sobrevivem ao câncer. Embora o transplante de células-tronco hematopoéticas (TCTH) esteja associado à diverso grado de cardiotoxicidade, essas complicações têm sido mal caracterizadas. Objetivo: analisar o perfil de liberação de biomarcadores miocárdicos como potenciais marcadores subclínicos de cardiotoxicidade em pacientes submetidos ao TCTH. Material e método: estudo descritivo, analítico, prospectivo, transversal, unicéntrico, com recrutamento de pacientes encaminhados à policlínica de cardio-oncologia, com indicação de TCTH de outubro de 2018 a março de 2020. Foram realizados controles clínicos, eletrocardiográficos, bioquímicos e de imagem de acordo com o algoritmo de acompanhamento. Os valores evolutivos dos biomarcadores séricos foram comparados pelo teste de Friedman. A FEVE basal foi comparada com a de 3 meses após o TCTH usando o teste de Wilcoxon. Resultados: foram incluídos 19 pacientes, 37% mulheres, com idade de 43,8 ± 15,7 anos. Nenhuma mudança na LVEF foi detectada. Em nenhum caso foi observado um aumento de TnI. Os valores de BNP aumentaram um mês após o transplante (linha de base: 13,6 6,1-30,9; vs. primeiro mês: 38,9 16,3-120,0, p = 0,036), se detectou uma maior elevação nos pacientes que receberam antimetabólitos vs. outros medicamentos (linha de base: 13,6 ;6,1-30,9; vs. no primeiro mês: 67,0 ;21,3-174,0;, p = 0,039). O aumento do BNP não foi associado ao risco CV. Conclusão: a liberação do BNP após o TCTH é frequente (32% de nossos pacientes), podendo chegar a no máximo um mês, independente da FEVE. O subgrupo de pacientes que recebeu antimetabólitos apresentou maior liberação precoce de BNP.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Stroke Volume/radiation effects , Biomarkers , Hematopoietic Stem Cell Transplantation , Hematologic Neoplasms/drug therapy , Cardiotoxicity/diagnosis , Antimetabolites, Antineoplastic/adverse effects , Cross-Sectional Studies , Prospective Studies , Sex Distribution
5.
Braz. J. Pharm. Sci. (Online) ; 59: e23063, 2023. tab, graf
文章 在 英语 | LILACS | ID: biblio-1505837

摘要

Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells


Subject(s)
Animals , Male , Rats , Doxorubicin/administration & dosage , Camellia sinensis/adverse effects , Cardiotoxicity , Echocardiography/instrumentation , Hematologic Neoplasms/pathology , Electrocardiography/instrumentation , Antioxidants/pharmacology
6.
Braz. J. Pharm. Sci. (Online) ; 59: e21220, 2023. graf
文章 在 英语 | LILACS | ID: biblio-1439533

摘要

Abstract Exposure to methanol can cause serious consequences such as permanent visual disturbances and death. The heart tissue is highly vulnerable to ATP deficiency. Our study aimed to investigate whether exogenous ATP administration may alleviate methanol-induced ATP deficiency and subsequent oxidative damage in rat heart tissue. A total of 30 rats were divided into equal five groups; Healthy Group (HG), Methotrexate (MXG), Methanol (MeOH), Methotrexate+Methanol (MXM), and Methotrexate+Methanol+ATP (MMA) groups. We inhibited tetrahydrofolate synthesis by methotrexate to induce methanol toxicity. Methotrexate was administered to MXG, MXM, and MMA group animals for seven days with a catheter directly to the stomach at a 0,3 mg/kg dose per day. At the end of this period, % 20 methanol at a dose of 3 g/kg was administered to MeOH, MMA and MXM group animals. Immediately after methanol application, MMA group animals were injected with ATP at a 4 mg/kg dose intraperitoneally. Blood samples and heart tissues were used for biochemical analysis and histopathological examination. Co-exposure to methanol and methotrexate substantially exacerbated cardiac damage, indicating the potent cardiotoxic effects of methanol. However, the administration of exogenous ATP to MMA group animals brought biochemical oxidative damage parameters and histopathological findings closer to HG.


Subject(s)
Animals , Male , Rats , Adenosine Triphosphate/analysis , Methanol/adverse effects , Cardiotoxicity/classification
7.
Med. lab ; 27(2): 111-122, 2023. Tabs
文章 在 西班牙语 | LILACS | ID: biblio-1435407

摘要

Introducción. Las emulsiones lipídicas intravenosas (ELI) son unas emulsiones grasas no tóxicas con fosfolípidos, actualmente aprobadas para su uso en el tratamiento de intoxicaciones, específicamente en las producidas por anestésicos locales. El propósito de este estudio es la caracterización del uso de ELI en pacientes mayores de 18 años, que presentaron intoxicación por sustancias y medicamentos diferentes a anestésicos locales, en un hospital de alta complejidad de la ciudad de Medellín, durante el periodo comprendido entre 2015 y 2020. Metodología. Se realizó un estudio descriptivo, retrospectivo, de casos que recibieron ELI como tratamiento para su intoxicación. Se hizo revisión de las historias clínicas de la población objeto de estudio. Se recolectó información acerca de variables sociodemográficas, clínicas y paraclínicas, y de atención. Se hizo análisis univariado de las variables de interés. Resultados. Del total de 1.966 intoxicaciones, se incluyeron 51 (2,6 %) casos de intoxicación por sustancias y medicamentos diferentes a anestésicos locales, que recibieron la terapia con ELI entre 2015 y 2020. La mediana de edad de los participantes fue de 27 años. Un 74,5 % de los participantes presentó intoxicación por medicamentos. El promedio de la dosis de ELI recibida fue de 1.036 mL en 24 horas, dosis inferior a la calculada por kilo de peso que debían recibir, de 1.149 mL en promedio. Un 86,3 % (n=44) de los casos presentaron neurotoxicidad, y 76,5 % (n=39) presentaron cardiotoxicidad. La neurotoxicidad mejoró en el 34,7 % y la cardiotoxicidad en el 59,1 % de los individuos que recibieron terapia con ELI. Conclusión. La aplicación de las ELI se hizo en personas en su mayoría intoxicadas por antipsicóticos, hombres, jóvenes; menos de la mitad tenía compromiso de la ventilación, y hubo mejoría en la cardiotoxicidad y neurotoxicidad. Hubo una diferencia entre la dosis recibida y la que debían recibir ajustada por el peso


Introduction. Intravenous lipid emulsions (IVLE) are non-toxic fatty emulsions with phospholipids, currently approved for use in the treatment of poisoning, specifically those produced by local anesthetics. The purpose of this study is to characterize the use of IVLE in patients over 18 years of age, who presented intoxication by substances and medications other than local anesthetics, in a high complexity hospital in the city of Medellín, during the period between 2015 and 2020. Methodology. A retrospective descriptive study was carried out on cases that received IVLE as a treatment for their poisoning. The clinical records of the study population were reviewed. Information was collected about sociodemographic, clinical and paraclinical variables, and care. Univariate analysis of the variables of interest was performed. Results. Of the total of 1,966 poisonings, 51 (2.6%) cases caused by substances and medications other than local anesthetics, received ELI therapy between 2015 and 2020 and were included in the study. The median age of the participants was 27 years. 74.5% of the participants presented drug poisoning. The average IVLE dose received was 1,036 mL in 24 hours, a lower dose than the one calculated per kilo of weight, which had been on average 1,149 mL. 86.3% (n=44) of the cases presented neurotoxicity, and 76.5% (n=39) presented cardiotoxicity. Neurotoxicity improved in 34.7% and cardiotoxicity in 59.1% of individuals receiving ELI therapy. Conclusion. The application of IVLE was made in people mostly poisoned by antipsychotics, men, young people, less than half had compromised ventilation, and there was improvement in cardiotoxicity and neurotoxicity. There was a difference between the dose received and the one they should have received adjusted for weight


Subject(s)
Humans , Fat Emulsions, Intravenous , Poisoning , Mortality , Neurotoxicity Syndromes , Electrocardiography , Cardiotoxicity
8.
Journal of Integrative Medicine ; (12): 302-314, 2023.
文章 在 英语 | WPRIM | ID: wpr-982683

摘要

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.


Subject(s)
Humans , Aconitine/chemistry , Cardiotoxicity , Sand , Alkaloids/toxicity , Arrhythmias, Cardiac/drug therapy , Diterpenes/toxicity
9.
文章 在 中文 | WPRIM | ID: wpr-1008738

摘要

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.


Subject(s)
Animals , Humans , Medicine, Chinese Traditional/adverse effects , Cardiotoxicity , Induced Pluripotent Stem Cells , Arrhythmias, Cardiac/chemically induced , Myocytes, Cardiac , Organoids , Drugs, Chinese Herbal/adverse effects
10.
Av. enferm ; 40(2): 307-319, 01/05/2022.
文章 在 西班牙语 | LILACS, BDENF, COLNAL | ID: biblio-1371003

摘要

Introducción: a nivel mundial, cada año cerca de 300.000 niños entre 0 y 19 años son diagnosticados con cáncer. El porcentaje de supervivientes va en aumento, llegando a 80% en países desarrollados y 60% en América Latina. Sin embargo, la expectativa y la calidad de vida de estas personas pueden verse comprometidas ante el desarrollo de cardiotoxicidad, un efecto adverso asociado al uso de algunos agentes antineoplásicos, como los antracíclicos. Objetivo: resaltar los aspectos clínicos relevantes para la prevención, detección oportuna, tratamiento y seguimiento de la cardiotoxicidad secundaria a la administración de antraciclinas durante la infancia. Síntesis de contenido: reflexión teórica que presenta consideraciones clínicas relevantes para guiar las acciones de enfermería y del equipo multidisciplinario en la atención y el cuidado de la salud cardiovascular de los supervivientes de cáncer a cualquier edad. Es importante destacar que en población pediátrica la única estrategia efectiva de prevención primaria para cardiotoxicidad por antraciclinas es la administración de dexrazoxano, mientras que la prevención secundaria debe incluir detección oportuna, control y seguimiento de las alteraciones de la función cardíaca y de los factores de riesgo cardiovascular. Por su parte, la prevención terciaria se centra en el control de la enfermedad y el manejo farmacológico. Conclusiones: no existe un tratamiento estándar para la cardiotoxicidad inducida por quimioterapia o radioterapia, siendo el objetivo principal de este tipo de tratamientos prevenir o retrasar la remodelación del ventrículo izquierdo. Todos los supervivientes requieren seguimiento vitalicio y búsqueda activa de signos de cardiotoxicidad, siendo fundamental la acción conjunta de diferentes profesionales y la consolidación de los servicios de cardio-oncología.


Introdução: em todo o mundo, a cada ano cerca de 300.000 pessoas entre 0 e 19 anos de idade são diagnosticadas com câncer. A porcentagem de sobreviventes aumentou e atingiu a cifra de 80% nos países desenvolvidos e 60% na América Latina; no entanto, a expectativa e a qualidade de vida podem ser comprometidas devido ao desenvolvimento de cardiotoxicidade, um efeito adverso associado ao uso de alguns agentes antineoplásicos, como os antracíclicos. Objetivo: destacar os aspectos clínicos relevantes para a prevenção, a detecção oportuna, o tratamento e o monitoramento da cardiotoxicidade secundária à administração de antraciclinas na infância. Síntese de conteúdo: reflexão teórica que apresenta as considerações clínicas relevantes para orientar as ações da enfermagem e da equipe multiprofissional na assistência e no cuidado à saúde cardiovascular do sobrevivente de qualquer idade. É importante observar que, na população pediátrica, a única estratégia eficaz de prevenção primária da cardiotoxicidade das antraciclinas é a administração de dexrazoxano; enquanto a prevenção secundária deve incluir a detecção oportuna, o controle e o acompanhamento de alterações da função cardíaca e dos fatores de risco cardiovascular; a prevenção terciária se concentra no controle da doença e no manejo farmacológico. Conclusões: não existe um tratamento-padrão para a cardiotoxicidade induzida por quimioterapia ou radioterapia, seu principal objetivo é prevenir ou retardar a remodelação ventricular esquerda. Todos os sobreviventes necessitaram de acompanhamento vitalício e busca ativa de sinais de cardiotoxicidade, sendo essencial a ação conjunta de diferentes profissionais e a consolidação dos serviços de cardio-oncologia.


Introduction: Every year, nearly 300,000 children aged 0 to 19 are diagnosed with cancer worldwide. The percentage of survivors has increased significantly, reaching 80% in developed countries and 60% in Latin America. However, the life expectancy and quality of life of these individuals can be severely compromised in the face of the development of cardiotoxicity, an adverse effect associated with the use of antineoplastic agents such as anthracyclics. Objective: To highlight relevant clinical aspects for the prevention, timely detection, treatment and follow-up of cardiotoxicity secondary to the administration of anthracyclines during childhood. Content synthesis: Theoretical reflection that presents relevant clinical considerations to guide the actions of nursing professionals and the interdisciplinary teams in charge of providing cardiovascular health care to cancer survivors at any age. We emphasize that the only effective primary prevention strategy for anthracycline cardiotoxicity in the pediatric population is the administration of dexrazoxane, while secondary prevention should include timely detection, control, and follow-up of cardiac function alterations and cardiovascular risk factors, and tertiary prevention must be focused on disease control and pharmacological management. Conclusions: There is no standard treatment for chemotherapy or radiotherapy-in-duced cardiotoxicity, and the main objective of current treatment methods is to prevent, or delay, left ventricular remodeling. All survivors require life-long monitoring and an active search for signs of cardiotoxicity, where the joint action of different professionals and the consolidation of cardio-oncology services becomes essential.


Subject(s)
Humans , Survivors , Cardiotoxicity , Heart Failure
11.
Int. j. cardiovasc. sci. (Impr.) ; 35(2): 214-219, Mar.-Apr. 2022. tab
文章 在 英语 | LILACS | ID: biblio-1364976

摘要

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.


Subject(s)
Animals , Male , Rats , Radiation-Protective Agents/therapeutic use , Plant Oils/therapeutic use , Nigella sativa , Oxidative Stress/drug effects , Heart/radiation effects , Antioxidants/therapeutic use , Plants, Medicinal , Radiation-Protective Agents/analysis , Rats, Inbred Strains , Rats, Wistar , Oxidative Stress/radiation effects , Plant Preparations/therapeutic use , Cardiotoxicity/drug therapy , Heart/drug effects , Phytotherapy
12.
Int. j. cardiovasc. sci. (Impr.) ; 35(2): 220-229, Mar.-Apr. 2022. tab, graf
文章 在 英语 | LILACS | ID: biblio-1364988

摘要

Abstract Background Cardiotoxicity is the main complication related to cancer therapy. Studies indicate that global longitudinal strain is an early detector of subclinical dysfunction of the left ventricle, preceding the decline in ejection fraction (EF). However, the reproducibility of such methodology has not been tested outside specialized centers. Objectives To assess the frequency of subclinical cardiotoxicity and to compare global longitudinal strain and EF measurements during the clinical course of patients undergoing chemotherapy for breast cancer. Methods This was an observational prospective study of 78 adult women who underwent serial echocardiograms (baseline and 1, 3, and 6 months after the beginning of chemotherapy), to evaluate biplane and 3D EF and global longitudinal strain. Cardiotoxicity and subclinical dysfunction were defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. Statistical significance was set at p < 0.05. Results The mean age of the patients was 50.1 ± 11.48 years. The frequency of subclinical cardiotoxicity (defined by global longitudinal strain) was 14.9% after 30 days of chemotherapy, 16.7% after 3 months, and 19.7% after 6 months, compared to 4.5%, 3%, and 6.6%, respectively, when clinical cardiotoxicity was determined according to EF. The group that developed subclinical cardiotoxicity by 30 days (group A) had a higher frequency of clinical cardiotoxicity at 3 months (p=0.028) and a lower mean biplane EF after 30 days (p= 0.036) than the group that showed no evidence of subclinical cardiotoxicity (group B). Conclusion Subclinical cardiotoxicity was frequent and began early, being associated with a drop in EF during the clinical course.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Breast Neoplasms/drug therapy , Ventricular Dysfunction, Left/etiology , Cardiotoxicity/etiology , Stroke Volume/drug effects , Ventricular Dysfunction, Left/diagnostic imaging , Cardiotoxicity/diagnostic imaging , Antineoplastic Agents/adverse effects
13.
文章 在 中文 | WPRIM | ID: wpr-928190

摘要

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.


Subject(s)
Animals , Rats , Cardiotoxicity , Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal/toxicity , Hormones , Metabolomics
14.
文章 在 中文 | WPRIM | ID: wpr-927949

摘要

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.


Subject(s)
Animals , Mice , Antioxidants/pharmacology , Cardiotoxicity , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Tripterygium
15.
文章 在 中文 | WPRIM | ID: wpr-927907

摘要

Cardiotoxicity is smong the main safety problems of drugs in clinical application. In recent years, traditional Chinese medicine has been gradually emphasized and studies on the evaluation of cardiac safety and prevention of cardiotoxicity of Chinese medicine have been on the rise, particularly the cardiotoxic Chinese medicine or the Chinese medicine components targeting cardiotoxicity. As for the research methods for cardiac safety evaluation of Chinese medicine, this review introduces the related clinical indexes and cell and animal models. As to the improvement of heart safety, this study reviews the material basis and mechanism of cardiotoxic Chinese medicines as well as the alleviation of cardiotoxicity by controlling the content of toxic compounds and changing dosage form, processing method, and compatibility of Chinese medicine. In addition, the effective components and mechanisms of prescriptions and active compounds in Chinese medicine for preventing and treating cardiotoxicity induced by chemotherapeutic drugs in recent years were summarized. This review is expected to serve as a reference for cardiac safety evaluation and clinical rational application of Chinese medicine.


Subject(s)
Animals , Cardiotoxicity/prevention & control , Drugs, Chinese Herbal , Medicine, Chinese Traditional
16.
文章 在 英语 | WPRIM | ID: wpr-928966

摘要

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.


Subject(s)
Humans , Anthracyclines/adverse effects , Cardiotoxicity/etiology , Drug Combinations , Drugs, Chinese Herbal/adverse effects
17.
Braz. J. Pharm. Sci. (Online) ; 58: e19245, 2022. graf
文章 在 英语 | LILACS | ID: biblio-1374573

摘要

Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.


Subject(s)
Animals , Female , Mice , Doxorubicin/adverse effects , Nanoparticles/classification , Ficusin/analysis , Blotting, Western/instrumentation , Cardiotoxicity/complications , Antioxidants/adverse effects
18.
Niterói; s.n; 2022. 136 p.
学位论文 在 葡萄牙语 | LILACS, BDENF | ID: biblio-1510228

摘要

Introdução: O câncer é responsável por 13% das causas de óbitos no mundo, sendo o de mama a primeira causa de mortes em mulheres no Brasil. Apesar dos benefícios da quimioterapia, estudos têm identificado efeitos cardiotóxicos a curto e longo prazo em mulheres com câncer de mama. Diante disso, a avaliação e manejo do enfermeiro de mulheres com câncer de mama submetidas a quimioterapia é fundamental para prevenção e reconhecimento precoce destes efeitos. Apesar disso, ainda não existem protocolos assistenciais de enfermagem para acompanhamento de mulheres com câncer de mama. Objetivo: Validar o conteúdo do Protocolo Assistencial de Enfermagem para Mulheres com Câncer de Mama submetidas à Quimioterapia Cardiotóxica. Método: Estudo metodológico realizado em três etapas: adaptação do conteúdo e modelo de um protocolo assistencial de enfermagem para pacientes adultos submetidos à terapia oncológica cardiotóxica para utilização com mulheres com câncer de mama de acordo com Appraisal of Guidelines for Research & Evaluation (AGREE II); avaliação da qualidade do protocolo por quatro enfermeiras especialistas na área de oncologia (02) e cardiologia (02). Foi utilizada uma escala likert de 7 pontos para avaliação. As médias foram calculadas de acordo com as notas dos especialistas em cada domínio proposto; validação do conteúdo do protocolo quanto a clareza, pertinência e relevância por 19 enfermeiros assistenciais com análise dos dados pelo índice de validação do conteúdo e análise de concordância pelo teste de Gwet. Foram realizados ajustes no protocolo para atender as sugestões dos experts e por fim, o protocolo foi validado por consenso com experts na área. Resultados: As quatro pesquisadoras atribuíram média de superior a cinco de acordo com os critérios avaliados no AGREEII. A avaliação da clareza, pertinência e relevância do protocolo obteve índice de validação de conteúdo global superior a 0,9 em todos os critérios (p˂0,001) por enfermeiros da prática assistencial. Por último, foi realizado um comitê de especialistas formado por enfermeiros pesquisadores e enfermeiros assistenciais na área de cardiologia e oncologia que, por consenso em duas reuniões, realizaram uma revisão e a validação do conteúdo do protocolo. Conclusão: O protocolo assistencial de enfermagem para mulheres com câncer de mama irá contribuir para uma prática de enfermagem pautada em evidências científicas, facilitando a identificação e manejo de sinais e sintomas cardiotóxicos, prevenindo complicações cardiovasculares e contribuindo para a documentação e informação sobre estes efeitos em mulheres com câncer de mama.


Introduction: Cancer is responsible for 13% of the causes of death in the world, with breast cancer being the leading cause of death in women in Brazil. Despite the benefits of chemotherapy, studies have identified short- and long-term cardiotoxic effects in woman with breast cancer. In this scenario, the nurse's assessment and management of woman with breast cancer undergoing chemotherapy is essential for prevention and early recognition of these effects. However, there are no nursing care protocols for monitoring women with breast cancer. Objectives: Validate the content of the Nursing Care Protocol for Women with Breast Cancer undergoing Cardiotoxic Chemotherapy. Method: Methodological study carried out in three stages: adaptation of the nursing care protocol for adult patients undergoing cardiotoxic cancer therapy for women with breast cancer according to the Appraisal of Guidelines for Research & Evaluation (AGREE II); protocol quality assessment by four specialist nurses in the fields of oncology (02) and cardiology (02). A 7-point Likert scale was used for evaluation. The averages were calculated according to the experts' scores in each proposed domain; validation of protocol content regarding clarity, suitability and relevance by 19 oncology care nurses with data analysis using the content validation index and agreement analysis using the Gwet test. Adjustments were made to the protocol to answer the researchers' suggestions and, finally, the protocol was validated by consensus with experts in the field. Results: The four researchers attributed an average of more than five according to the criteria evaluated in the AGREE. The assessment of clarity, suitability and relevance of the protocol obtained a global content validation index higher than 0.9 in all criteria (p˂0.001) by nurses working in the care practice. Finally, a committee of specialists formed by research nurses and clinical nurses in the area of cardiology and oncology was created and, by consensus in two meetings, carried out a review and validation of the protocol content. Conclusion: A nursing care protocol for women with breast cancer will contribute to a nursing practice based on scientific evidence, facilitating the identification and management of cardiotoxic signs and symptoms, preventing cardiovascular complications and contributing to the documentation and information about these effects in women with breast cancer


Subject(s)
Breast Neoplasms , Nursing , Guidelines as Topic , Cardiotoxicity
19.
In. Graña, Andrea; Calvelo, Estela; Fagúndez, Yohana. Abordaje integral del paciente con cáncer: atención desde la medicina y especialidades. Montevideo, Cuadrado, 2022. p.178-181.
专著 在 西班牙语 | LILACS, UY-BNMED, BNUY | ID: biblio-1418004
20.
In. Graña, Andrea; Calvelo, Estela; Fagúndez, Yohana. Abordaje integral del paciente con cáncer: atención desde la medicina y especialidades. Montevideo, Cuadrado, 2022. p.181-186.
专著 在 西班牙语 | LILACS, UY-BNMED, BNUY | ID: biblio-1418010
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