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Chinese Journal of Oncology Prevention and Treatment ›› 2013, Vol. 5 ›› Issue (2): 105-109.doi: 10.3969/j.issn.1674-5671.2013.02.05

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Effects of trimetazidine on myocardial energy metabolism after adriamycin chemotherapy in a nude mouse breast cancer model

  

  • Online:2013-06-25 Published:2013-06-27

Abstract:  Objective To investigate the myocardial protective effects of trimetazidine(TMZ) and its mechanism of action by re-searching the drug′s influence on myocardial energy metabolism after adriamycin(ADM) chemotherapy in a nude mouse breast cancer model. Methods Nude mice(n=27) with breast cancer were randomly divided into three groups:group A(control group) received saline(10 ml/kg) injections into the abdominal cavity,and groups B and C received ADM injections(2.5 ml/kg) into the abdominal cavity twice a week for 4 weeks. From the third week,group C was given TMZ by gavage 20 mg/(kg·d),once a day for 14 days; groups A and B received the same amounts of saline at the same times. Mice were anesthetized on the second day after the last administration.At three time points(before gavage,T1;before anesthesia,T2;30 min afer anesthesia,T3),blood(0.2 ml) and myocardial tissue specimens were taken from mice in all three groups.Serum levels of cTnI and activity of myocardial mitochondrial long-chain 3-ketoacyl coenzyme A thiolase(3-KAT) were measured by enzyme-linked immunosorbent assay(ELISA).Levels of adenosine triphosphate(ATP) and adenosine diphosphate(ADP) in myocardial tissue were determined by high performance liquid chromatography(HPLC). Results  ① At T1,serum cTnI level was higher in groups B and C than in group A(P<0.05),but there was no significant difference between groups B and C(P>0.05).At T2 and T3,the cTnI level was significantly lower in group C than in group B(P<0.05).Serum cTnI level in group A did not vary significantly across all three time points(P>0.05).In group B,in contrast,serum cTnI level was higher at T3 than at T1 and T2(P<0.05).In group C,the cTnI level was significantly higher at T1 than at T2 or T3,and T2 was significantly lower than at T1 and T3(P<0.05).② ATP and ADP levels were significantly different among the three groups(P<0.05);these levels were higher in group C than in group B(P<0.05).③ 3-KAT levels were significantly different among the three groups(P<0.05);the level was lower in group C than in group B(P<0.05). Conclusion  Trimetazidine protects against myocardial injury induced by ADM chemotherapy in a nude mouse breast cancer model.It exerts these protective effects by improving myocardial energy metabolism,inhibiting myocardial mitochondrial 3-KAT activity and improving ATP and ADP levels in myocardial tissue.

Key words: Breast neoplasms, Trimetazidine, Adriamycin, Nude mice, Myocardial protection, Energy metabolism