Efeitos do exercício físico e ácido ursólico em rins de ratos submetidos à modelo de inflamação por lipopolissacarídeo

Abstract

Chronic low-grade inflammation is a central component of the pathophysiology of chronic kidney disease (CKD), promoting endothelial dysfunction, fibrosis, and the progressive loss of renal function. Among the molecular pathways involved, purinergic signaling emerges as a central mediator between inflammatory stress and renal metabolic responses. In this dissertation, the role of exercise training (ET) as a modulator of these responses was addressed from two complementary perspectives. The first study, a narrative literature review, gathered evidence on the effects of ET on the inflammatory profile of CKD, highlighting its ability to modulate inflammatory cytokines and investigating the involvement of the purinergic system in this context. The second, an experimental study, investigated both ET and ursolic acid (UA)—a phytochemical pentacyclic triterpene derived from various plants. For this purpose, an animal model was utilized, employing 65 male Wistar rats subjected to a resistance ET protocol and treated with UA or saline solution orally for six weeks. During the final week of the protocol, lipopolysaccharides (LPS) were administered daily via intraperitoneal injection to induce an inflammatory response. The animals were distributed into eight groups: saline (SAL, n = 9), ET (n = 8), UA (n = 8), ET + UA (n = 8), LPS (n = 8), ET + LPS (n = 8), UA + LPS (n = 8), and ET + UA + LPS (n = 8). Subsequently, the animals were euthanized, and kidneys and serum were collected for analysis of the purinergic system, irisin levels, and biochemical parameters. The results demonstrated that exercise training stood out as the most effective intervention in restoring purinergic homeostasis. The combination of ET and UA potentiated these effects, reinforcing the synergistic nature between the metabolic action of exercise and the anti-inflammatory bioactivity of the triterpene. Together, both studies sustain that exercise training plays a pivotal role in modulating systemic and renal inflammation, also acting on purinergic signaling as an interface pathway between metabolism and the immune response. The association with natural bioactive compounds, such as ursolic acid, emerges as a promising approach for developing non-pharmacological strategies aimed at the prevention and treatment of inflammatory-based renal injuries.