ABC | Volume 112, Nº2, February 2019

Original Article Badavi et al Trimetazidine effects on diabetic hearts Arq Bras Cardiol. 2019; 112(2):173-178 Figure 2 – Hypertrophy value in control (C), diabetic (D) and diabetic treated with TMZ (T10) groups eight weeks after treatment in the rats. The results were presented as mean ± SD. # p < 0.05 compared with control group, ***p < 0.001 compared to the untreated diabetic group. 70 60 50 40 30 20 10 0 Heart/body Weight (mg/g) # *** C D T10 Animal groups Table 1 – Hemodynamic parameters in the heart Groups C D T10 P value D VS. C P value T10 VS. D Heart rate (beats/min) 268 ± 27.99 198 ± 41.21 263 ± 35.02 0.002 ## 0.006 ** LVSP (mmHg) 75 ± 20.91 60.78 ± 16.76 79.75 ± 10.16 0.041 # 0.028 * LVDP (mmHg) 74.37 ± 18.76 56 ± 18.37 74.25 ± 9.93 0.030 # 0.031 * RPP (mmHg) 14965 ± 5582 10184 ± 4589 14099 ± 3859 0.041 # 0.049 * Max +dp/dt(mmHg) 2294 ± 255.27 1035 ± 370.33 1727 ± 410.60 < 0.001 ### 0.001 ** Min -dp/dt (mmHg) -1220 ± 229.09 -594.77 ± 210 -962 ± 194 < 0.001 ### 0.002 ** (Mean ± SD, n = 8) in control (C), diabetic (D) and diabetic treated with TMZ (T10), (one-way ANOVA followed by LSD post hoc test). LVSP: left ventricular systolic pressure; LVDP: left ventricular diastolic pressure; RPP: rate pressure product. Table 2 – Antioxidant enzymes activities Groups C D T10 P value D vs. C P value T10 vs. D SOD (U/dl) 8.46 ± 1.51 5.86 ± 0.69 7 ± 1.54 0.002 ## 0.049 * CAT (U/ dl) 10.52 ± 0.60 1.90 ± 4.08 10.71 ± 0.50 0.002 ## < 0.001*** GPx (U/ dl) 28.50 ± 2.67 13.22 ± 0.95 24.03 ± 1.73 < 0.001 ### < 0.001*** (Mean ± SD, n = 8) in control (C), diabetic (D) and diabetic treated with TMZ (T10), (one-way ANOVA followed by LSD post hoc test). SOD: superoxide dismutase. CAT: catalase; GPx: glutathione peroxidase. which result in decreased anti-oxidant level and anti‑oxidant defense system. 32 Increased level of fatty acid oxidation in the diabetic heart leads to lipid accumulation and cardiac hypertrophy. 33 Reduction in fatty acid oxidation and oxidative stress by TMZ treatment can partly attribute to improvement of cardiac hypertrophy. Previous studies have indicated that SOD level reduced in type 1 diabetes and it is mostly demonstrated that increased reactive oxygen species (ROS) negatively associated with the enzyme antioxidant values such as SOD and GPx. 34 SOD quickly alters O 2 to H 2 O 2 , which is further destroyed via GPx and CAT. The antioxidant enzyme levels are sensitive to the oxidative stress, and enhanced or reduced values have been indicated in various pathologies in which an increase of ROS is a cause or result of the disorder such as diabetes. 35,36 In addition, superoxide anions and ROS have also been indicated to be contributed to cardiac hypertrophy resulted from various stimuli; therefore, SOD is a primary defense against oxidative stress that involves in the hypertrophy of the heart. 37 Our findings indicated that SOD and CAT levels in hearts from TMZ treated diabetic rats was significantly higher than that in the untreated diabetic animals. GPx values was slightly but not significantly more in the hearts from TMZ treated diabetic animals compared to the diabetic rats. Taken together, these findings indicated that the diabetic rats showed hypertrophy and dysfunction in the heart as well as increased cardiac oxidative damage in comparison with the control animals, showing that these undesirable factors are connected. TMZ probably improved these factors by antioxidant effects. Based on the results of present study, more studies require to be carried out to assessment mechanisms involved in the improvement of hypertrophy and cardiovascular disorders resulted from diabetes using TMZ treatment. Conclusions All these observations show that TMZ treatment contributes to the improvement of impaired function and electrical activity as well as hypertrophy of the heart in diabetic cardiomyopathy in rats. Improvements observed in TMZ treatment is associated with decrease oxidative stress. 176