Author + information
In the present study, we investigated the effect and possible mechanism of action of trimetazidine in pirarubicin-induced myocardial damage.
Thirty-six Wistar rats were randomly divided into control, model, and treatment groups. The rats in the model and treatment groups were injected through the vena caudalis with pirarubicin (2.5 mg/kg once a week) for six weeks. The control group rats were injected in the same manner with 0.9% NaCl for 6 weeks. The rats in the treatment group received an intragastric infusion of trimetazidine at 5.4 mg/kg/d for 8 weeks, while those in the control and model groups received infusions of 0.9% NaCl. At the end of the experiment, we measured the levels of superoxide dismutase, cardiac enzymes, and free radical mediators. Echocardiography parameters were measured using an ultrasonic diagnostic instrument. Myocardial tissue was examined using light and electron microscopy.
The levels of myoglobin, troponin, and alanine aminotransferase (ALT) were lower in the treatment group than in the model group (P < 0.05). Malondialdehyde (MDA) and nitric oxide (NO) levels were lower after treatment than in the model group (P < 0.05), and nonprotein sulfhydryl (NPSH) and superoxide dismutase (SOD) levels were higher in the treated animals than in the model group (P < 0.05). The left ventricular ejection fraction (EF) and fractional shortening (FS) were higher in the rats treated with trimetazidine than in the model group (P < 0.05), and the left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs) were lower in the rats treated with trimetazidine than in the model group (P < 0.05). In the model group, the structure of myocardial cells was severely damaged, they were arranged in a disorderly manner, and myocardial myofilament dissolution and fracturing were observed. In the treatment group, the structure of myocardial cells was orderly, and the structure of the myocardium was essentially preserved.
Treatment with trimetazidine reduced mitochondrial damage and relieved myocardial injury, indicating that trimetazidine exerted a protective effect on cardiomyocytes that were exposed to pirarubicin. The mechanism underlying this effect may be related to its antioxidative activities.