Impacto do exercício físico sobre as alterações hepáticas, bioquímicas, oxidativas, inflamatórias e metabólicas associadas a privação de sono em camundongos Swiss

Abstract

Sleep deprivation (SD) is a stressor capable of inducing behavioral, neuroendocrine, inflammatory, and metabolic dysfunctions. Significant hepatic repercussions may occur secondary to SD. This study aimed to investigate whether chronic aerobic physical exercise can prevent or attenuate the deleterious effects induced by 72 hours of total sleep deprivation. We used male young adult Swiss mice, aged 90 to 150 days. Animals were allocated into four experimental groups: Control, Exercise (EXE), SD, and Exercise + SD (EXE+SD). The study included behavioral, biochemical, oxidative, hepatic histological, and metabolomic evaluations. Behavioral assessment revealed that SD increased immobility time in the forced swim test, reduced exploration in the Y-maze, and decreased entries into the open arms of the elevated plus maze, indicating impairments in memory, exploratory behavior, and anxiety-like states, respectively. Biochemical analyses demonstrated that SD increased serum levels of AST, ALT, urea, creatinine, triglycerides, and total cholesterol, along with significant reductions in albumin and glucose. These effects were accompanied by hepatic increases in TNF-α, IL-1β, IL-6, MCP-1, INF-γ, MDA, protein carbonylation, nitrite, and MPO activity, as well as reductions in GSH, SOD, and CAT. Histological analysis revealed mild diffuse inflammatory infiltration in the SD group. Hepatic metabolomics indicated that SD induced significant alterations in several metabolites, including reductions in dehydroascorbate, salicylate, fructose, and glucose. Physical exercise positively modulated the metabolic profile, restoring pathways related to amino acid, glyoxylate, glutathione, arginine, and proline metabolism. The

EXE+SD group exhibited an intermediate profile, with partial or full reversal of SD- induced damage. These findings suggest that chronic aerobic physical exercise plays a

protective role against the behavioral, inflammatory, redox, and metabolic hepatic alterations induced by sleep deprivation. Such findings have translational implications for the prevention of SD-associated metabolic disorders.