Physical exercise as a modulator of the purinergic system in the control of sarcopenia in individuals with chronic kidney disease on hemodialysis

Abstract

The word sarcopenia derives from the Greek terms "sarx" for meat and "penia" for loss, thus being used to define reductions in muscle mass, muscle strength, and lower physical performance that compromise, mainly, the elderly population. Its high negative impact on patients' quality of life encourages the production and publication of new studies that seek to find methods to prevent and reverse cases of loss of muscle mass and strength. Furthermore, the high prevalence of sarcopenia in patients with chronic kidney disease (CKD) is closely related to its pathophysiology, which consists of a state of increased protein catabolism and decreased muscle tissue synthesis. Also considering the inflammatory nature of CKD and sarcopenia, the purinergic system has been an important target of studies, which seek to relate it to the two previous conditions. This system achieves anti-inflammatory action by inhibiting, through adenosine, pro-inflammatory factors such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO), as well as by releasing anti-inflammatory substances such as interleukin-10 (IL-10). Simultaneously, the purinergic system presents pro-inflammatory activity, signaled by adenosine triphosphate (ATP), which occurs through the activation of T cells and the release of pro-inflammatory factors such as those mentioned above. Therefore, the ability of this system to act on inflammatory processes can promote positive and negative changes in the clinical aspect of patients with CKD and/or sarcopenia. Furthermore, it appears that there is a correlation between the practice of repeated physical exercise with the clinical improvement and in the quality of life of these patients, presenting a decrease in the levels of C-reactive protein (CRP), NTPDase, and the pro-inflammatory cytokine IL-6, such as increases in IL-10 resulting from modulation of the purinergic system. In this way, the present article seeks to evaluate the effect of physical exercise as a modulator of the purinergic system in the control of sarcopenia in patients with CKD on hemodialysis, in order to trace a relationship that can bring benefits both for biological markers and for quality of life of these patients.

Keywords: Chronic renal insufficiency; Inflammation; Purinergic; Sarcopenia.

Fig. 1

Mechanisms of muscle loss in patients with CKD. IL-6 and TNF-y activate myostatin, which binds with ActR-IIB. This complex, in turn, activates atrogens that translate into muscle loss. Created with BioRender.com

Fig. 2

Cycle of cell destruction and further release of reactive oxygen species. The enzymes SOD, catalase, and glutathione peroxidase act as antioxidants. CAT, catalase. SOD, superoxide dismutase. GLUT, glutathione peroxidase. Blurry stains: molecules that act in cellular damage, such as ROS, H2O2, and superoxide radicals. Yellow thunder: cellular damage

Fig. 3

Anti-inflammatory pathways involved during physical exercise. During physical activity, myocytes release IL-6, which in this context has anti-inflammatory activity by blocking the activities of IL-1 and TNF-α. In addition, the catecholamines released during exercise, especially adrenaline, also have anti-inflammatory roles

Fig. 4

During muscle contraction, myocytes release myostatin, which has the function of inhibiting muscle gain. On the other hand, several other cytokines with an antagonistic effect to that of myostatin are also released, promoting muscle mass gain

Fig. 5

Inflammatory activity of the purinergic system. ATP, when binding to P2X7 receptors, causes sources of cytokines, such as skeletal muscle fibers and leukocytes, to release pro-inflammatory cytokines, such as IL-1β and IL-6