Trimetazidine as a modifier of doxorubicin+cyclophosphamideinduced hyperdyslipidemia

Abstract

Aim. The present work aimed at studying the proatherogenic potential of doxorubicin-cyclophosphamide (AC) chemotherapy regimen while simultaneously substantiating the use of trimetazidine as a modifier of the changes induced.Material and Methods. The fundamental, randomized, controlled, experimental in vivo study was conducted. To perform the experimental work, 80 inbred Wistar rats were randomly divided into four groups with equal numbers of animals in each group. The course dosages doxorubicin, cyclophosphamide, and trimetazidine were 15, 150, and 42 mg/kg, respectively. The experiment lasted for 14 days. Trimetazidine was chosen as a probable stabilizer of endothelial functioning.Results. The deviations of the following parameters were evaluated in the framework of this study: total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins. Coronary index and atherogenic index (CA) were also analyzed as prognostic indicators. Statistically significant intergroup differences were recorded in lipid profiles (one-way ANOVA, p < 0.0001) two weeks after beginning the AC chemotherapy regimen. It is worthy of note that the AC chemotherapy regimen caused destabilization of all studied parameters of cholesterol metabolism while trimetazidine showed statistically and pathogenetically significant mild hypolipidemic effect. The study showed that the concentration of CA in group 2 was higher by 187.4 and 172.8%, and the values of coronary risk index (CRI) were higher by 115.8 and 113.9% than the corresponding parameters in groups 1 and 4, respectively. Comparative analysis of groups 3 and 2 showed that the use of TMZ was associated with decreases in CA by 55.5% and in CRI by 44.2% (Tukey’s post-hoc test, p < 0.05).Conclusions. (1) AC chemotherapy regimen was an inducer of atherogenic hyperdyslipidemia, and (2) trimetazidine had a hypolipidemic effect.