In this editorial,we review the article published in World J Gastrointest Oncol 2019,11:1031-1042.We specifically focus on the occurrence,clinical characteristics,and risk factors of fluoropyrimidine drug-related card...In this editorial,we review the article published in World J Gastrointest Oncol 2019,11:1031-1042.We specifically focus on the occurrence,clinical characteristics,and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors.Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors,the incidence and mortality rates of treatment-related car-diotoxicity have been increasing,severely impacting the survival and prognosis of cancer patients.Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors,including gastrointestinal tumors,and they represent the second largest class of drugs associated with cardiotoxicity.However,there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.展开更多
Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At...Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At present,the mechanism of doxorubicin induced cardiotoxicity has not been fully clarified.Reducing cardiotoxicity and improving the scope of clinical application have become the focus of research in recent years.This paper reviews the mechanism of doxorubicin cardiotoxicity and the prevention and treatment of doxorubicin cardiotoxicity with traditional Chinese medicine,in order to provide reference for the combined application of doxorubicin.展开更多
Background: Cardiac toxicity is currently defined as a symptomatic decrease in Left Ventricular Ejection Fraction (LVEF) of more than 5% or an asymptomatic decrease of at least 10% to a value of under 50% in repeated ...Background: Cardiac toxicity is currently defined as a symptomatic decrease in Left Ventricular Ejection Fraction (LVEF) of more than 5% or an asymptomatic decrease of at least 10% to a value of under 50% in repeated evaluations on conventional transthoracic echocardiogram (TTE), as well as a Global Longitudinal Strain (GLS) value Aims: To highlight using GLS rather than modified Simpson 2D-LVEF for the evaluation of long-term cardiotoxicity. Case Presentation: The case concerns a 73-year-old female patient with a history of breast cancer chemotherapy and anthracyclines-based therapy who presented symptoms of late cardiac toxicity related to the chemotherapeutic treatment. In the following years, the patient remained asymptomatic with a 2D-LVEF of 48%, dilation of the left atrium was found, and the reservoir phase strain was severely decreased. Conclusion: The preferred method for evaluating cardiovascular complications associated with chemotherapy is the TTE, which is performed prior to the start of treatment, during therapy, and in the follow-up. Myocardial deformation as a predictor of cardiotoxicity allows the identification of subclinical heart failure.展开更多
Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart fa...Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.展开更多
AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these chan...AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes.METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDGPET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the preand posttherapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium.RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than change in cardiac SUVmean between pre-and post-chemotherapy PET) in 1 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both preand post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the followup 18 F-FDG-PET study. Group A (n = 8): showed an increase in cardiac 18 F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac 18 F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac 18 F-FDG uptake in the posttherapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m 2 ) received during the time of the follow-up FDG-PET study was 256. 25, 250 and 137.5, respectively.CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.展开更多
Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity ...Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.展开更多
Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient’s management and outcome.The coexistence of cancer and cardiac disease in th...Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient’s management and outcome.The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents.Left ventricular dysfunction is the most typical manifestation and can lead to heart failure.Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage,but it identifies a late manifestation of myocardial injury.Early non-invasive imaging techniques are needed for the diagnosis and monitoringof cardiotoxic effects.Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment,greater attention is focused on new nuclear cardiologic techniques,which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation.The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage,focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.展开更多
Cardio-oncology is a discipline based on early screening,monitoring,and treating chemotherapy-induced cardiotoxicity.There are many chemotherapeutics known for their cardiac toxic effects,including fluoropyrimidines.F...Cardio-oncology is a discipline based on early screening,monitoring,and treating chemotherapy-induced cardiotoxicity.There are many chemotherapeutics known for their cardiac toxic effects,including fluoropyrimidines.Fluoropyrimidine represents the cornerstone of many types of cancer and each year almost two million cancer patients undergo this treatment.Fluoropyrimidine-induced cardiotoxicity can be manifested in several forms,from angina pectoris to sudden death.This paper is a review of how the cardiotoxicity of fluoropyrimidines is presented,the mechanisms of its occurrence,its diagnosis,and management.展开更多
This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which ind...This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which indicated that thymol was the major constituent representing 33.896%.Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent,thymol,at doses 250 and 100 mg/kg b.w./every other day,respectively,by oral gavage for the same period.Thyme oil and thymol markedly ameliorated the raised levels of serum urea,uric acid,and creatinine in DOX-administered rats.They also reduced the elevated activities of serum CK-MB and LDH.Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats,thereby reflecting its more potent effect on kidney and heart functions.Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft,inflammatory cells infiltration,protein cast in lumina of the renal tubule,and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol;thyme oil was more effective.In addition,DOX-induced deleterious heart histological alterations,including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes,and edema,were remarkably reduced by treatment with thyme oil and thymol.Thus,it can be concluded that DOX could induce marked toxicity in kidney and heart,and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.展开更多
Background: As more patients survive cancer chemotherapy, problems associated with the late complications of therapy have become increasingly apparent;late doxorubicin cardio-myopathy being one of the most pressing. T...Background: As more patients survive cancer chemotherapy, problems associated with the late complications of therapy have become increasingly apparent;late doxorubicin cardio-myopathy being one of the most pressing. The relationship between initial dose, schedule employed, and etiology are still not well defined. This study attempts to clarify some of these issues. Methods: Patients receiving large total doses of doxorubicin by schedules designed to minimize peak drug levels were monitored in regard to their cardiac status for up to 31 years following completion of doxorubicin therapy. A computer program predicting the amount of doxorubicin retained by the heart vs. schedules employed was devised with the predictions of the computer program being compared to the clinical findings. Results: 1365 patients receiving doses of doxorubicin greater than 610 mgm./M2 were monitored for up to 31 years following completion of such therapy. No patient developed unequivocal clinical and pathologic evidence of a doxorubicin related cardiomyopathy. Knowing that human cardio-myocytes contain enzymes capable of neutralizing doxorubicin, a computer program predicted that by increasing their efficiency, the schedules employed substantially l decreased the relative amount of drug retained by the heart, findings compatible with both animal experiments and clinical results. Conclusions: administration of doxorubicin by schedules in which peak plasma levels of drug were minimized resulted in marked decreases in both acute and long-term cardiac toxicity;believed to be due to potentiation of myocardial enzymes capable of inactivating the drug.展开更多
Doxorubicin(Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms...Doxorubicin(Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.展开更多
Objective: This work was designed to determine the productive effect of grape seed proanthocynadine extract (GSPE) and Vitamin E against Doxorubicin (DOX) induced myocardial toxicity in 50 male. Wister rates were divi...Objective: This work was designed to determine the productive effect of grape seed proanthocynadine extract (GSPE) and Vitamin E against Doxorubicin (DOX) induced myocardial toxicity in 50 male. Wister rates were divided in five groups. The 1st group was untreated and served as a control. The 2nd group was treated with DOX only, the 3rd group was pretreated with GSPE, the 4th group was pretreated with Vitamin E, and the 5th group was pretreated with GSPE and Vitamin E. DOX was administered by single i.p (Intraperitonial) injection of 15 mg/kg/body weight to induce cardio toxicity and Vitamin E was administered at a dose of 400 IU/kg/bodyweight/day, p.o (per oral) for 10 days prior to DOX administration [1]. GSPE was given at a dose of 150 mg/kg/bodyweight/ day, p.o (per oral) for 10 days before treatment with DOX. After 2 weeks experimental period, blood samples and heart tissues were taken from all groups. The general observations, mortality, histopathology, biomarker enzymes like Lactate Dehydrogenase (LDH), Creatine Phosphokinase (CPK), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Antioxidants such as Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA) were monitored after 2 weeks of the last dose. Results: Administration of DOX caused cardiomyopathy associated with an antioxidant deficiency. Pretreatment with GSPE and Vitamin E significantly (P < 0.01) protected the myocardium from the toxic effects of DOX by reducing the elevated level of biomarkers and diagnostic enzymes like LDH, CPK, AST, and ALT to normal levels. GSPE and Vitamin E increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Conclusion: These results suggest a cardioprotective effect of GSPE and Vitamin E due to its antioxidant properties.展开更多
OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxici...OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based validation.METHODS Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch clamping.Subsequently,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch clamping.RESULTS We have tested the cardiotoxicity of monomers extracted from various medical herbs.Mitragynine is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East Asia.As a popular stimulant,it has been associated with a number of acute fatal incidences.We observed a typical torsadogenic hazard of mitragynine.It exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion channels.Moreover,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low cardiotoxicity.It exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·L-1.At 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in hPSC-CMs.CONCLUSION We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs validation.This new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potential pro-arrhythmic risk.展开更多
Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperi...Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.展开更多
OBJECTIVE Aconitine(ACO)as the main active component in Aconitum carmichaelii debeaux(family Ranunlaceae),has highly toxicity in heart and the mechanisms are not clear yet.Paeoniflorin(PF),the main chemical ingredient...OBJECTIVE Aconitine(ACO)as the main active component in Aconitum carmichaelii debeaux(family Ranunlaceae),has highly toxicity in heart and the mechanisms are not clear yet.Paeoniflorin(PF),the main chemical ingredient in Herbaceous peony,can protect heart hurt by antioxidant,vasodilator effect and other effects.In this study,we focused on investigating the mechanism of PF reducing the cardiotoxicity of ACO.METHODS We chose H9c2 cells as experimental subject.MTT,Western blotting and real-time PCR were used to measure cell proliferation,apoptosis,ion channels and oxidative stress.RESULTS Cell proliferation in ACO+PF group was significantly increased compared with ACO group;the ratio with Bcl-2 and Bax and the level of p53 were upregulated by PF,while the level of caspase-3 was lightly reduced.The expression of SCN5A mRNA significantly was increased in ACO+PF group,while the expres⁃sion of RyR2 and Cx43 mRNA was dropped.Compared with ACO group,extracellular LDH and intracellular MDA were highly decreased,while intracellular SOD was regulated.CONCLUSION Cardiotoxicity of ACO in H9c2 cells was signifi⁃cantly decreased by PF.展开更多
Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin...Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin and 10-6mol/L adriamycin + 10 8mol/I. CGRP. Lactate dehydrogenase (LDH ) activity in the mediumand the contents of malondialdehyde (MDA ). calcium. and magnesium in the myocardial cells were assayed.Results: In the adriamycin group, LDH activity in medium and calcium, MDA contents in myocardial cells weresignificantly increased compared with those in control group, and magnesium content in the myocardial cells wassignificantly reduced. In the adriamycin group. there was a positive correlation between LDH activity in themedium and MDA content in the myocardial cells. Meanwhile, in the adriamycin + CGRP group,- CGRP mightsignificantly reduce the leakage of LDH from myocardial cells, lessen the increase in calcium and MDA contentsand prevent the loss of magnesium. Conclusion: CGRP may inhibit adriamycin induced acute cardiotoxicity byinhibiting lipid peroxidation, attenuating calcium overload, magnesium loss, and protecting enzyme activity.展开更多
Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubM...Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.展开更多
Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mecha...Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.展开更多
BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiot...BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure.Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress echocardiogram.She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment course.She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms.Approximately two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure.Echocardiogram showed an ejection fraction of 5%-10%with severe biventricular failure.Despite attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of hospitalization.The autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity effusions.CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo.Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice.We have reviewed literature and recent advances in the prediction and prevention of AIC.Although risk factors currently identified can help stratify patients who need closer monitoring,there are limitations to our current understanding and further research is needed in this field.展开更多
Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature...Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature retrieval(SinoMed),ten thousand Data knowledge service system(WanFang Data),VIP full-text database(VIP),PubMed,MedLine and the cochrane library were searched from inception to 1st,December,2020.Relevant combined TCM and Western medicine on cardiotoxicity randomized controlled trials(RCTs)were collected.The risk of bias in included RCTs were evaluated according to the Cochrane Handbook.The required indicators were extracted and included in RevMan5.4 analysis.Results:A total of 2844 patients were included in 37 RCTs.The results of meta-analysis showed that compared with the control group,TCM treatment group could alleviate the effect of anthracycline on ventricular ejection function,reduce the effect of anthracycline chemotherapy drugs in lowering left ventricular ejection fraction(WMD=6.44,95%CI 0.38 to 12.50,P=0.04),reduce the effect of anthracycline chemotherapy in increasing left ventricular end diastolic diameter(WMD=-0.59,95%CI-0.74 to-0.44,P<0.00001),reduce the effect of anthracycline chemotherapy drugs in increasing left ventricular end systolic diameter(WMD=-0.47,95%CI-0.60 to-0.34,P<0.00001),and reduce the effect of anthracyclines on troponin I(WMD=-0.19,95%CI-0.23 to-0.16,P<0.00001),troponin T(WMD=-0.02,95%CI-0.03 to-0.01,P<0.00001)and brain natriuretic peptide(WMD=-32.21,95%CI-58.21 to-6.22,P=0.02).Conclusion:The existing evidence can prove that TCM has a protective effect on cardiotoxicity caused by anthracycline chemotherapy,maintaining left ventricular ejection fraction and ventricular diameter,controlling the level of myocardial injury markers,and alleviating cardiac injury.展开更多
文摘In this editorial,we review the article published in World J Gastrointest Oncol 2019,11:1031-1042.We specifically focus on the occurrence,clinical characteristics,and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors.Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors,the incidence and mortality rates of treatment-related car-diotoxicity have been increasing,severely impacting the survival and prognosis of cancer patients.Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors,including gastrointestinal tumors,and they represent the second largest class of drugs associated with cardiotoxicity.However,there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.
基金National Natural Science Foundation of China(No.82074419)"Double First-Class"Key Research Project of Gansu Provincial Education Department(No.GSSYLxM-05)。
文摘Doxorubicin is an anthracycline antibiotic.As a broad-spectrum antitumor drug,it is widely used in clinic.However,doxorubicin is dose-dependent and shows obvious cardiotoxicity,which limits its clinical application.At present,the mechanism of doxorubicin induced cardiotoxicity has not been fully clarified.Reducing cardiotoxicity and improving the scope of clinical application have become the focus of research in recent years.This paper reviews the mechanism of doxorubicin cardiotoxicity and the prevention and treatment of doxorubicin cardiotoxicity with traditional Chinese medicine,in order to provide reference for the combined application of doxorubicin.
文摘Background: Cardiac toxicity is currently defined as a symptomatic decrease in Left Ventricular Ejection Fraction (LVEF) of more than 5% or an asymptomatic decrease of at least 10% to a value of under 50% in repeated evaluations on conventional transthoracic echocardiogram (TTE), as well as a Global Longitudinal Strain (GLS) value Aims: To highlight using GLS rather than modified Simpson 2D-LVEF for the evaluation of long-term cardiotoxicity. Case Presentation: The case concerns a 73-year-old female patient with a history of breast cancer chemotherapy and anthracyclines-based therapy who presented symptoms of late cardiac toxicity related to the chemotherapeutic treatment. In the following years, the patient remained asymptomatic with a 2D-LVEF of 48%, dilation of the left atrium was found, and the reservoir phase strain was severely decreased. Conclusion: The preferred method for evaluating cardiovascular complications associated with chemotherapy is the TTE, which is performed prior to the start of treatment, during therapy, and in the follow-up. Myocardial deformation as a predictor of cardiotoxicity allows the identification of subclinical heart failure.
基金All authors are supported by the Victorian Government’s Operational Infrastructure Support ProgramSBS is supported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipRM is supported by a National Health and Medical Research Council Senior Research Fellowship(Grant No.1078985).
文摘Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
文摘AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes.METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDGPET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the preand posttherapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium.RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than change in cardiac SUVmean between pre-and post-chemotherapy PET) in 1 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both preand post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the followup 18 F-FDG-PET study. Group A (n = 8): showed an increase in cardiac 18 F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac 18 F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac 18 F-FDG uptake in the posttherapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m 2 ) received during the time of the follow-up FDG-PET study was 256. 25, 250 and 137.5, respectively.CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.
基金Supported by National Natural Science Foundation of China,No.82070285 and No.81701861.
文摘Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.
文摘Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient’s management and outcome.The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents.Left ventricular dysfunction is the most typical manifestation and can lead to heart failure.Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage,but it identifies a late manifestation of myocardial injury.Early non-invasive imaging techniques are needed for the diagnosis and monitoringof cardiotoxic effects.Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment,greater attention is focused on new nuclear cardiologic techniques,which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation.The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage,focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.
文摘Cardio-oncology is a discipline based on early screening,monitoring,and treating chemotherapy-induced cardiotoxicity.There are many chemotherapeutics known for their cardiac toxic effects,including fluoropyrimidines.Fluoropyrimidine represents the cornerstone of many types of cancer and each year almost two million cancer patients undergo this treatment.Fluoropyrimidine-induced cardiotoxicity can be manifested in several forms,from angina pectoris to sudden death.This paper is a review of how the cardiotoxicity of fluoropyrimidines is presented,the mechanisms of its occurrence,its diagnosis,and management.
文摘This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which indicated that thymol was the major constituent representing 33.896%.Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent,thymol,at doses 250 and 100 mg/kg b.w./every other day,respectively,by oral gavage for the same period.Thyme oil and thymol markedly ameliorated the raised levels of serum urea,uric acid,and creatinine in DOX-administered rats.They also reduced the elevated activities of serum CK-MB and LDH.Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats,thereby reflecting its more potent effect on kidney and heart functions.Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft,inflammatory cells infiltration,protein cast in lumina of the renal tubule,and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol;thyme oil was more effective.In addition,DOX-induced deleterious heart histological alterations,including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes,and edema,were remarkably reduced by treatment with thyme oil and thymol.Thus,it can be concluded that DOX could induce marked toxicity in kidney and heart,and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.
文摘Background: As more patients survive cancer chemotherapy, problems associated with the late complications of therapy have become increasingly apparent;late doxorubicin cardio-myopathy being one of the most pressing. The relationship between initial dose, schedule employed, and etiology are still not well defined. This study attempts to clarify some of these issues. Methods: Patients receiving large total doses of doxorubicin by schedules designed to minimize peak drug levels were monitored in regard to their cardiac status for up to 31 years following completion of doxorubicin therapy. A computer program predicting the amount of doxorubicin retained by the heart vs. schedules employed was devised with the predictions of the computer program being compared to the clinical findings. Results: 1365 patients receiving doses of doxorubicin greater than 610 mgm./M2 were monitored for up to 31 years following completion of such therapy. No patient developed unequivocal clinical and pathologic evidence of a doxorubicin related cardiomyopathy. Knowing that human cardio-myocytes contain enzymes capable of neutralizing doxorubicin, a computer program predicted that by increasing their efficiency, the schedules employed substantially l decreased the relative amount of drug retained by the heart, findings compatible with both animal experiments and clinical results. Conclusions: administration of doxorubicin by schedules in which peak plasma levels of drug were minimized resulted in marked decreases in both acute and long-term cardiac toxicity;believed to be due to potentiation of myocardial enzymes capable of inactivating the drug.
文摘Doxorubicin(Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.
文摘Objective: This work was designed to determine the productive effect of grape seed proanthocynadine extract (GSPE) and Vitamin E against Doxorubicin (DOX) induced myocardial toxicity in 50 male. Wister rates were divided in five groups. The 1st group was untreated and served as a control. The 2nd group was treated with DOX only, the 3rd group was pretreated with GSPE, the 4th group was pretreated with Vitamin E, and the 5th group was pretreated with GSPE and Vitamin E. DOX was administered by single i.p (Intraperitonial) injection of 15 mg/kg/body weight to induce cardio toxicity and Vitamin E was administered at a dose of 400 IU/kg/bodyweight/day, p.o (per oral) for 10 days prior to DOX administration [1]. GSPE was given at a dose of 150 mg/kg/bodyweight/ day, p.o (per oral) for 10 days before treatment with DOX. After 2 weeks experimental period, blood samples and heart tissues were taken from all groups. The general observations, mortality, histopathology, biomarker enzymes like Lactate Dehydrogenase (LDH), Creatine Phosphokinase (CPK), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Antioxidants such as Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA) were monitored after 2 weeks of the last dose. Results: Administration of DOX caused cardiomyopathy associated with an antioxidant deficiency. Pretreatment with GSPE and Vitamin E significantly (P < 0.01) protected the myocardium from the toxic effects of DOX by reducing the elevated level of biomarkers and diagnostic enzymes like LDH, CPK, AST, and ALT to normal levels. GSPE and Vitamin E increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Conclusion: These results suggest a cardioprotective effect of GSPE and Vitamin E due to its antioxidant properties.
基金The project supported by National Medical Research Council(NMRC CG12Aug09&NMRC EDG10may050)National Research Foundation(NRF2008-CRP003-02)of Singapore and Ministry of Science,Technology and Innovation Malaysia(Sciencefund Grant to Tan Mei Lan)
文摘OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de pointes.Current single ion channel(hERG)-based assay generates-30% false results.The aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based validation.METHODS Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch clamping.Subsequently,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch clamping.RESULTS We have tested the cardiotoxicity of monomers extracted from various medical herbs.Mitragynine is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East Asia.As a popular stimulant,it has been associated with a number of acute fatal incidences.We observed a typical torsadogenic hazard of mitragynine.It exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion channels.Moreover,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low cardiotoxicity.It exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·L-1.At 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in hPSC-CMs.CONCLUSION We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs validation.This new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potential pro-arrhythmic risk.
文摘Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.
文摘OBJECTIVE Aconitine(ACO)as the main active component in Aconitum carmichaelii debeaux(family Ranunlaceae),has highly toxicity in heart and the mechanisms are not clear yet.Paeoniflorin(PF),the main chemical ingredient in Herbaceous peony,can protect heart hurt by antioxidant,vasodilator effect and other effects.In this study,we focused on investigating the mechanism of PF reducing the cardiotoxicity of ACO.METHODS We chose H9c2 cells as experimental subject.MTT,Western blotting and real-time PCR were used to measure cell proliferation,apoptosis,ion channels and oxidative stress.RESULTS Cell proliferation in ACO+PF group was significantly increased compared with ACO group;the ratio with Bcl-2 and Bax and the level of p53 were upregulated by PF,while the level of caspase-3 was lightly reduced.The expression of SCN5A mRNA significantly was increased in ACO+PF group,while the expres⁃sion of RyR2 and Cx43 mRNA was dropped.Compared with ACO group,extracellular LDH and intracellular MDA were highly decreased,while intracellular SOD was regulated.CONCLUSION Cardiotoxicity of ACO in H9c2 cells was signifi⁃cantly decreased by PF.
文摘Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin and 10-6mol/L adriamycin + 10 8mol/I. CGRP. Lactate dehydrogenase (LDH ) activity in the mediumand the contents of malondialdehyde (MDA ). calcium. and magnesium in the myocardial cells were assayed.Results: In the adriamycin group, LDH activity in medium and calcium, MDA contents in myocardial cells weresignificantly increased compared with those in control group, and magnesium content in the myocardial cells wassignificantly reduced. In the adriamycin group. there was a positive correlation between LDH activity in themedium and MDA content in the myocardial cells. Meanwhile, in the adriamycin + CGRP group,- CGRP mightsignificantly reduce the leakage of LDH from myocardial cells, lessen the increase in calcium and MDA contentsand prevent the loss of magnesium. Conclusion: CGRP may inhibit adriamycin induced acute cardiotoxicity byinhibiting lipid peroxidation, attenuating calcium overload, magnesium loss, and protecting enzyme activity.
基金This research was supported by the National Natural Science Foundation of China(81530100 and 81822049).
文摘Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.
基金Fund Project:National natural science foundation of China(No.81573915)。
文摘Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.
文摘BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure.Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress echocardiogram.She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment course.She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms.Approximately two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure.Echocardiogram showed an ejection fraction of 5%-10%with severe biventricular failure.Despite attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of hospitalization.The autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity effusions.CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo.Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice.We have reviewed literature and recent advances in the prediction and prevention of AIC.Although risk factors currently identified can help stratify patients who need closer monitoring,there are limitations to our current understanding and further research is needed in this field.
基金National Key Research and Development Program(No.2018YFC1704901)。
文摘Objective:To systematically evaluate the therapeutic effect of TCM on cardiotoxicity induced by anthracycline chemotherapy to provide clinical guidance.Methods:China hownet database(CNKI),Chinese biomedical literature retrieval(SinoMed),ten thousand Data knowledge service system(WanFang Data),VIP full-text database(VIP),PubMed,MedLine and the cochrane library were searched from inception to 1st,December,2020.Relevant combined TCM and Western medicine on cardiotoxicity randomized controlled trials(RCTs)were collected.The risk of bias in included RCTs were evaluated according to the Cochrane Handbook.The required indicators were extracted and included in RevMan5.4 analysis.Results:A total of 2844 patients were included in 37 RCTs.The results of meta-analysis showed that compared with the control group,TCM treatment group could alleviate the effect of anthracycline on ventricular ejection function,reduce the effect of anthracycline chemotherapy drugs in lowering left ventricular ejection fraction(WMD=6.44,95%CI 0.38 to 12.50,P=0.04),reduce the effect of anthracycline chemotherapy in increasing left ventricular end diastolic diameter(WMD=-0.59,95%CI-0.74 to-0.44,P<0.00001),reduce the effect of anthracycline chemotherapy drugs in increasing left ventricular end systolic diameter(WMD=-0.47,95%CI-0.60 to-0.34,P<0.00001),and reduce the effect of anthracyclines on troponin I(WMD=-0.19,95%CI-0.23 to-0.16,P<0.00001),troponin T(WMD=-0.02,95%CI-0.03 to-0.01,P<0.00001)and brain natriuretic peptide(WMD=-32.21,95%CI-58.21 to-6.22,P=0.02).Conclusion:The existing evidence can prove that TCM has a protective effect on cardiotoxicity caused by anthracycline chemotherapy,maintaining left ventricular ejection fraction and ventricular diameter,controlling the level of myocardial injury markers,and alleviating cardiac injury.
