The apoptosis process could impose significantly by hyperglycemia. According to in silico language processing and high throughput raw data analysis, we recognized hub molecular mechanisms involved in the pathogenesis of diabetic hearts and suggested a new pharmaceutical approach for declining myocardial programed cell death. Fifty male Sprague-Dawley rats were classified into five groups: healthy rats as control, diabetic rats, diabetic combined resistance/endurance training, diabetic rats which How to cite this article: Heydarnia, E., Taghian, F., Jalali Dehkordi, K., & Moghadasi, M. (2022). Regular combined training and vitamins modulated the apoptosis process in diabetic rats: Bioinformatics analysis of heart failure's differential genes expression network correlated with anti-apoptotic process.

Background: Diabetes leads to metabolic disorders in the heart by creating free radicals and compromising the antioxidant defense system. Objectives: The aim of this study was to investigate the effect of eight weeks of combined training and supplementation with antioxidant vitamins E and C on the antioxidant capacity of heart tissue in streptozotocin-induced diabetic rats. Methods: Sixty male Sprague Dawley rats (weight: 280 ± 20 g; age: 2-3.5 months) were randomly divided into five groups as follows: (1) healthy control, (2) diabetic control, (3) diabetic + combined training, (4) diabetic + supplementation, and (5) diabetic + combined training + supplementation. The combined training protocol included incremental resistance training of 5 - 45% of rat weight on the ladder, and incremental endurance training was performed for 10 - 30 minutes at an intensity of 40 - 75% of maximum speed on the treadmill during eight weeks. The heart tissue was extracted and antioxidant enzymes were measured by lab spectroscopy 48 hours after the last training session. Data was analyzed using independent samples t-test, two-way ANOVA, and Bonferroni test (P ≤ 0.05). Results: The induction of diabetes significantly reduced glutathione (GSH; P = 0.001), glutathione peroxidase (GPx; P = 0.004), and superoxide dismutase (SOD; P = 0.001). In the treatment groups, a significant increase in the effect size of GSH (in the training and supplementation group: 6.45, training group: 3.18, and supplementation group: 2.92), GPX (in the training and supplementation group: 0.03, supplementation group: 0.023, and training group: 0.021), and SOD (in the training and supplementation group: 556.68, training group: 405.70, and supplementation group: 401.46 nmol / mL) was observed. Conclusions: Antioxidant supplementation and training by reducing the harmful effects of hyperglycemia strengthen the antioxidant defense system of heart tissue, and the combination of the two interventions is more effective than either alone.