Effect of traditional Chinese medicine on anthracycline-induced cardiotoxicity in animal models:A systematic review and metaanalysis

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.

Anthracycline-induced cardiotoxicity:A case report and review of literature

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.

Screening of Myocardial Cardiotoxicity Induced by Anticancer Chemotherapy and the Importance of Global Longitudinal Strain

Introduction: The improvement of survival in patients with cancer and the expansion of therapeutic options have led to the emergence of a new profile of cardiotoxicity, specifically associated with antimitotic agents. Our study aimed to assess the incidence of chemotherapy-induced myocardial toxicity in patients with cancer. Patients and Methods: We conducted a looking-forward longitudinal cohort study including all patients admitted to the Cardiology departments of Aristide le Dantec Hospital and Dalal Jamm National Hospital Centre for apre-chemotherapy check-up. The included patients did not undergo any pre-existing cardiopathy. Results: Over a period of two years ranging from January 2019 to December 2021, a total of 37 patients were included in the study. Notably, there was a female predominance (92%) with an average age of 49.7 years ± 13.69. Breast cancer accounted for 70% of the neoplasms. Laboratory findings revealed moderate anemia in 19 patients (51%). At inclusion, the left ventricle (LV) was of normal size (LV diastole at 44.46 ± 4.97 mm). The systolic function of the left ventricle was normal in all patients, with an average ejection fraction (EF) of 63.1% ± 5.80 and a mean global longitudinal strain (GLS) of −20.4% ± 2.58. The most commonly used agents were anthracyclines. During follow-up, 3 patients (8.1%) developed clinical symptoms of left heart failure, and LV dysfunction on echocardiography was observed in 5 (13.5%) patients, with a significant decrease in EF Conclusion: The incidence of cardiac toxicity is not negligible, hence the importance of early screening. Strain imaging is an essential tool that should be performed as part of the assessment before chemotherapy and re-evaluated during treatment.

Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors

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.

Long Term Follow-Up of Cardiotoxicity in Breast Cancer Treatment: A Case Report

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.

Research progress on cardiotoxicity mechanism of doxorubicin and prevention and treatment of traditional Chinese medicine

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.

Enhanced myocardial fluorodeoxyglucose uptake following Adriamycin-based therapy: Evidence of early chemotherapeutic cardiotoxicity?

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.

IGF1-PI3K-induced physiological cardiac hypertrophy:Implications for new heart failure therapies,biomarkers,and predicting cardiotoxicity

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.

Evaluation of Epirubicin-induced Cardiotoxicity by Two-dimensional Strain Echocardiography in Breast Cancer Patients

The value of two-dimensional strain echocardiography for assessing left ventricular regional systolic function in breast cancer patients who were treated with epirubicin was evaluated. A total of 116 breast cancer patients were divided into 3 groups： Thirty-eight patients in group A were given epirubicin （Epi） of 120-340 mg/m^2, 42 patients in group B received epimbicin of≥ 360 mg/m^2, and 36 patients after surging without chemotherapy served as the control group C. High frame rate two-dimensional images were recorded from apical long-axis view, four-chamber view, two-chamber view of left ventricle. Peak systolic strain of left ventricular subendocardial myocardium was measured using two-dimensional strain software. The conventional echocardiographic parameters were also obtained. Conventional echocardiography showed there was no significant changes in conventional echocardiographic parameters among the three groups （P〉0.05）. Two-dimensional strain echocardiography revealed that the peak systolic strain of left ventricular subendocardial myocardium in group A was reduced in some segments as compared with the controls （P〈0.05）. The peak systolic strain of left ventricular subendocardial myocardium in group B was reduced significantly as com- pared with group C （P〈0.05）, but that was reduced in group B just in some of the segments as compared with group A （P〈0.05）. It was concluded that two-dimensional strain echocardiography could early and sensitively display the effects of epirubicin-induced cardiotoxicity on the systolic function of left ventricular subendocardial myocardium, and early monitor the epirubicin-induced cardiotoxicity.

Nuclear imaging in detection and monitoring of cardiotoxicity

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.

Antipsychotics cardiotoxicity:What's known and what's next

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.

The Relation between the Initial Type of Schedule Used to Administer Doxorubicin and Long-Term Doxorubicin Cardiotoxicity

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.

Thyme oil and thymol abrogate doxorubicin-induced nephrotoxicity and cardiotoxicity in Wistar rats via repression of oxidative stress and enhancement of antioxidant defense mechanisms

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.

Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

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.

Fluoropyrimidine-induced cardiotoxicity

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.

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

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.

A comprehensive cardiotoxicity assay by combining high-throughput multiple ion channel screening with human cardiomyocyte-based action potential validation

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.

Paeoniflorin reduces cardiotoxicity of aconitine in H9c2 cells

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.

The inhibitory effect of calcitonin gene-related peptide on adriamycin induced acute cardiotoxicity in cultured myocardial cells

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.

Ciprofloxacin Cardiotoxicity and Hepatotoxicity in Humans and Animals

Ciprofloxacin is generally well tolerated;the most common adverse effects include gastro intestinal tract, central nervous system and hematological system effects. Recently rising cases of Ciprofloxacin associated toxicity have been reported. Experiment using animal models and clinical experience showed that Ciprofloxacin induced cardiotoxicity is marked by increase QT and QTC interval and prolonged action potential duration. This increases the risk of arrhythmia (tosarde de pointes). Ciprofloxacin induced cardiotoxic effect could be associated with blocking cardiac voltage—gated potassium channels particularly the rapid component (IKr) of the delayed rectifier potassium current. Drug interaction with inhibitors of Cytochrome P450 (CYP) mediated metabolism could be one of the underlying mechanisms. Several cases of Ciprofloxacin induced hepatoxicity have been also reported. These were characterized by extensive hepatocellular necrosis, mixed inflammatory infiltrate and abundant esinophils in the liver. Elevated liver enzymes which include serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gramma-glutamyltranferase and prolong prothrobin time were reported. The hepatotoxic effect of Ciprofloxacin as reported could be due to oxidative stress induced in the liver by Ciprofloxacin through the generation of oxidative radicals leading to depletion of protein content in hepatocytes as a consequence of nucleic acids diminution and DNA damage. This may lead to significant decrease in the number and degeneration in mitochondria which is responsible for energy supply. Conclusion: Ciprofloxacin induced cardiotoxicity and hepatotoxicity is relatively low in humans but patients’ liver and cardiac function may be considered before Ciprofloxacin use.