In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.
Animals ; Antibiotics, Antineoplastic ; adverse effects ; Antioxidants ; metabolism ; Cardiomyopathies ; chemically induced ; drug therapy ; Cardiotoxicity ; drug therapy ; Cyclooctanes ; therapeutic use ; Dexrazoxane ; therapeutic use ; Doxorubicin ; adverse effects ; Heart ; physiopathology ; Lignans ; therapeutic use ; Myocardium ; enzymology ; Polycyclic Compounds ; therapeutic use ; Rats ; Rats, Sprague-Dawley

The myocardial protective effects of endothelin antagonist in ischemic cardiomyopathy (ICMP), doxorubicin-induced cardiomyopathy (DOX) and pressure-overload hypertrophy by transverse aortic constriction (TAC) models have been predicted to be different. The objective of this experiment, therefore, is to evaluate the myocardial protective effect of tezosentan, an endothelin receptor antagonist, in various experimental heart failure models. Sprague-Dawley rats (6-8 weeks old, 200-300 g) were randomized to three experimental groups (n=30 each): ICMP; DOX; and TAC group. Each of these groups was randomly assigned further to the following subgroups (n=10 each): sham-operated ischemia-reperfusion subgroup (SHAM); tezosentan treated ischemia-reperfusion subgroup (Tezo); and tezosentan non-treated ischemia-reperfusion subgroup (N-Tezo). Total circulatory arrest was induced for 1 hr, followed by 2 hr of reperfusion. The left ventricular developed pressure, peak positive and negative first derivatives, and coronary blood flow were significantly different (P<0.05) among the SHAM, Tezo, and N-Tezo subgroups of the ICMP group at 30 min of reperfusion, but there were no statistically significant differences among the subgroups of the DOX and TAC groups. In conclusion, tezosentan, an endothelin receptor antagonist, showed myocardial protection effects only on the ischemic cardiomyopathy rat model, but not in the non-ischemic heart failure rat models.
Animals ; Cardiomyopathies/chemically induced/drug therapy/physiopathology ; Coronary Vessels/physiology ; Disease Models, Animal ; Doxorubicin/toxicity ; Heart Failure/*drug therapy/physiopathology ; Hypertrophy/drug therapy/physiopathology ; Male ; Pressure ; Pyridines/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptors, Endothelin/*antagonists & inhibitors/metabolism ; Reperfusion Injury/*drug therapy/physiopathology/surgery ; Tetrazoles/*therapeutic use ; Vasodilator Agents/*therapeutic use ; Ventricular Function, Left/physiology

AIM: To study the effect and probable mechanism of Qishen Yiqi Pills on adriamycin (ADR)-induced cardiomyopathy in mice. METHODS: Sixty-four mice were randomly divided into (1) the ADR group: saline (1 mL/100 g) administered every day by intragavage, ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks; (2) the ADR + Qishen Yiqi Pills I group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the beginning of the third week Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (3) the ADR + Qishen Yiqi Pills II group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the same time Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (4) the control group: saline (1 mL/100 g) administered every day by intragavage, saline (1 mL·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks. Six weeks later, cardiac function, myocardial pathology, and expression of Bcl-2 and Bax were evaluated. RESULTS: 1. The left ventricular diastolic diameter and the left ventricular systolic diameter were significantly increased (P < 0.05) and the left ventricular ejection fraction was significantly decreased (P < 0.05) in the ADR group, and the cardiac function of both the ADR + Qishen Yiqi Pills I group and the ADR + Qishen Yiqi Pills II group improved. 2. Myocardial morphologic observation showed that the myocardial fibers were disordered, there was cell edema, and gap widening in the ADR group. The degree of myocardial cell injury was reduced in the ADR + Qishen Yiqi Pills I group and ADR + Qishen Yiqi Pills II group compared with the ADR group. 3. The expression of Bax in the ADR group was significantly up-regulated, and the expression of Bcl-2 was significantly downregulated in the ADR group compared with the ADR + Qishen Yiqi Pills I group, the ADR + Qishen Yiqi Pills II group, and the control group (P < 0.05). CONCLUSIONS Qishen Yiqi Pills can effectively improve the cardiac function of ADR-induced cardiomyopathy, and the earlier it is used is better. The probable mechanism of action may be the inhibition of the apoptosis of myocardial cells.
Animals ; Apoptosis ; drug effects ; Cardiomyopathies ; chemically induced ; drug therapy ; genetics ; metabolism ; physiopathology ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Mice ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo study the effect of extract of Ginkgo biloba (Egb761) on doxorubicin-associated cardiotoxicity in patients with breast cancer (BC).

METHODSSixty BC patients in stage IV were randomly assigned to two groups, the control group was treated with chemotherapy, using 4 cycles of PA protocol alone and the treated group with the same chemotherapy and Egb761. Changes in electrocardiogram (ECG), myocardial enzyme spectrum (MES) and ultrasono-cardiogram (USCG) before and after treatment were observed.

RESULTSAfter treatment, the incidence of abnormal ECG was lower in the treated group than in the control group (6.7% vs 30.0%); significant differences were found between the two groups in the parameters of MES (P< 0.05); USCG showed significant difference between the two groups in left ventricular diastolic diameter (LVDd), left ventricular systolic diameter (LVDs), ratio of early and late diastolic transmitral peak flow velocity (E/A) and fractional shortening (FS), while there was no significant difference in ejection fraction (EF).

CONCLUSIONEgb761 is an ideal drug for preventing and reducing the acute doxorbincin-induced cardiotoxicity; it could also be helpful for alleviating the chronic cardiotoxicity.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carcinoma, Ductal, Breast ; drug therapy ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; administration & dosage ; adverse effects ; Female ; Ginkgo biloba ; chemistry ; Humans ; Middle Aged ; Phytotherapy ; Plant Extracts ; therapeutic use ; Treatment Outcome ; Ventricular Dysfunction, Left ; physiopathology ; prevention & control