Heart failure (HF) and type 2 diabetes mellitus (DM2) are prevalent diseases worldwide, and both can cause muscle atrophy. Both disorders are related to increased autophagy and apoptosis in muscle cells, consequently reducing muscle volume. Physical exercise associated with photobiomodulation seems promising to attenuate the skeletal muscle changes caused by HF and DM2.

To verify the influence of physical exercise and the association with photobiomodulation on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2.

18 male rats were divided into four groups: CT (not included in protocols), CT- (HF + DM2), EX+HF+D (HF + DM2 + aerobic exercise), and EX+HF+D+P (HF + DM2 + aerobic exercise + photobiomodulation). To induce DM2, streptozotocin (0.25 ml/kg, i.p.) was injected. To induce HF, coronary ligation was performed. After one week of disease induction, aerobic exercise, and photobiomodulation protocol were started for eight weeks. The protein expressions analyzed by the western blot were BAX, CASPASE-3, CASPASE-9, ANEXIN-V, P-ASK, MTOR, BECLIN-1, P62, LC3-I, LC3-II, NRF2 and P-AKT.

The apoptosis proteins BAX (p=0.13), CASPASE-3 (p=0.62), CASPASE-9 (p=0.20), ANEXIN-V (p=0.85), and P-ASK (p=0.71), as well as autophagy proteins - MTOR (p=0.71), BECLIN-1 (p=0.58), P62 (p=0.70) and LC3-II (p=0.16) did not show statistical significance among groups. EX+HF+D+P group expressed increased NRF2 (p=0.04), p-AKT (p=0.03), and LC3I (p=0.005) expression compared to the CT- group.

We demonstrated the positive effects of physical exercise associated with photobiomodulation, increasing the expression of proteins related to myocyte survival.

In this study, we observed an increase in Nrf2 levels in animals that performed physical exercise related to photobiomodulation, demonstrating a protective effect of the association of these two protocols on the gastrocnemius of animals with HF and DM. These results are relevant since there is a lack of therapeutic agents that may mitigate the muscle damage related to the association of DM and HF. Therefore, we suggest that the association between therapies can revert possible changes involving cell death.