SEVOFLURANE MEDIATED PROTECTION AGAINST HEPATIC ISCHEMIA-REPERFUSION INJURY IN ATHLETES: EXPLORING THE MICRORNA-182/TLR4/NF-ΚB PATHWAY

Abstract

Background: Sevoflurane (Sevo), a widely used inhalational anesthetic, has been recognized for its protective effects across various organs, offering potential therapeutic benefits in managing hepatic ischemia-reperfusion injury (HI/RI), a condition of interest within the athlete population due to its implications on physical health and performance. This study aims to delineate the mechanistic pathways through which Sevo mitigates HI/RI, focusing on its interaction with the microRNA-182/TLR4/NF-κB cascade, and to explore the potential implications for sports psychology and athlete health management. Method: In vivo mouse models of I/R injury were developed to assess the impact of Sevo on hepatic tissue integrity using Hematoxylin-eosin (HE) staining. Serum markers including aspartate-transaminase (AST), alanine-aminotransferase (ALT), lactic dehydrogenase (LDH), and the expressions of superoxide dismutase (SOD), malondialdehyde (MDA), NF-κB pathway-related genes, and apoptosis levels were measured to evaluate Sevo's effects. Results: Sevo pretreatment significantly ameliorated histological damage, hepatocyte apoptosis, inflammation, and oxidative stress in HI/RI models. Notably, Sevo was found to upregulate miR-182 expression, with its protective effects attenuated upon miR-182 inhibition through antagomir-182 injection. MiR-182 directly targeted toll-like receptor 4 (TLR4) gene, a key component of the TLR family, suggesting Sevo's mechanism of reducing TLR4/NF-κB pathway activation involves miR-182 upregulation. Conclusion: Sevo's hepatoprotective action against HI/RI involves downregulating the miR-182/TLR4/NF-κB signaling pathway, mitigating apoptosis, oxidative damage, and inflammation. These findings not only illuminate Sevo's underlying protective mechanisms but also propose its potential as a novel therapeutic approach for athletes experiencing hepatic I/R injury, with broader implications for enhancing physical health and psychological resilience in sports contexts.