Response of cardiac apoptosis proteins to eight-week aerobic training and caffeine supplementation in male Wistar rats

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

1 Department of Exercise Physiology, University of Kurdistan, Sanandaj, Iran

2 Department of Biological Sciences, Faculty of Basic Sciences, University of Kurdistan, Sanandaj, Iran.

3 Department of Physical Education and Sport Sciences, Mari.C. Islamic Azad University, Marivan, Iran,

4 Department of Exercise Physiology, Faculty of Humanities and Social Sciences, University of Kurdistan, Kurdistan, Iran.

Abstract

Background& purpose: Endurance exercise and caffeine consumption modulate cardiac cell signaling pathways; however, the interactive effects of these interventions on the expression of apoptosis-regulating proteins in myocardial tissue have not yet been fully elucidated. The present study aimed to investigate the effects of eight weeks of endurance training and caffeine supplementation on cardiac apoptosis factors (BAX, BCL2, P53, Caspase3, and miR-499) in male Wistar rats. Methods:Thirty-two rats were divided into four groups: control (ND), caffeine (ND+CAF), endurance training (ND+ET), and combined training + caffeine (ET+CAF). The caffeine groups received 6 mg/kg/day of caffeine via oral gavage. Endurance training was performed on a treadmill for eight weeks (five sessions per week), with intensity increasing from 12 m/min (15 min) in the first week to 27 m/min (60 min) by the eighth week. The relevant factors were measured using Western blot and Real time PCR methods. One Way-ANOVA test was used and Tukey's post hoc test was used to compare the two groups. Results: The results showed that the level of proapoptotic protein BAX was higher in the caffeine group, while it was lower in the endurance training group and the combination of training and caffeine group (P=0.001). Also, the level of antiapoptotic protein BCL2 was higher in the combination of training and caffeine group (P=0.001). The expression level of miR-499 in the endurance training group and the combination of training and caffeine group was higher than that in the control group (P=0.001), and caspase 3 was lower in all groups than in the control group (P=0.001), but it had no significant effect on P53 (P=0.873). Conclusion: endurance training effectively mitigates cardiac apoptosis, and when combined with caffeine supplementation, it enhances anti-apoptotic signaling—indicating a synergistic cardioprotective effect mediated by BCL-2 upregulation, miR-499 activation, and suppression of caspase-dependent apoptotic pathways.

Keywords

Main Subjects



Articles in Press, Accepted Manuscript
Available Online from 10 December 2025
  • Receive Date: 31 July 2025
  • Revise Date: 10 December 2025
  • Accept Date: 09 December 2025