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

Objective To investigate the myocardial protective effects of trimetazidine(TMZ) and its mechanism of action by researching 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(P0.05),but there was no significant difference between groups B and C(P0.05).At T2 and T3,the cTnI level was significantly lower in group C than in group B(P0.05).Serum cTnI level in group A did not vary significantly across all three time points(P0.05).In group B,in contrast,serum cTnI level was higher at T3 than at T1 and T2(P0.05).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(P0.05).② ATP and ADP levels were significantly different among the three groups(P0.05);these levels were higher in group C than in group B(P0.05).③ 3-KAT levels were significantly different among the three groups(P0.05);the level was lower in group C than in group B(P0.05). 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.