Impact of Exercise Training on Survival Rate and Neural Cell Death in Sepsis Through the Maintenance of Redox Equilibrium
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Sepsis-related deaths occur during both the early proinflammatory and the late immunosuppressive phases of the condition. The balance of pro- and anti-inflammatory responses is influenced by damaged cells that die via either proinflammatory necroptosis or anti-inflammatory apoptosis. Both forms of cell death may be mediated by reactive oxygen species (ROS) generated during the proinflammatory response. Recent evidence suggests that exercise training boosts antioxidative capacity and could offer protection against sepsis. Given these findings, we aimed to examine the impact of exercise training on neural cell death in the context of sepsis. Methods: We assessed the effectiveness of exercise in reducing ROS production and the inflammatory response using a cecal ligation and puncture (CLP)-induced sepsis model. Forty C57BL/6N male mice were randomly divided into 2 groups: control (CLP-Con; n=20) and experimental (CLP-Ex; n=20). Before the induction of sepsis by CLP, the CLP-Ex mice underwent interval training on a treadmill 3 days per week for 8 weeks. Each day involved 10 cycles of 2 minutes at 8 m/min and 2 minutes at 15 m/min. After the CLP procedure, we monitored the survival of 10 mice from each group over a 30-hour period. Results: The findings indicated that exercise training increased the survival rate among mice with CLP-induced sepsis by enhancing antioxidative capacity and delaying the transition from a hyperdynamic to an immunosuppressive state. Conclusions: Exercise training may delay the progression from the hyperdynamic state to the hypodynamic phase of sepsis by increasing antioxidant capacity and reducing apoptotic cell death.
Abstract
Purpose: Sepsis-related deaths occur during both the early proinflammatory and the late immunosuppressive phases of the condition. The balance of pro- and anti-inflammatory responses is influenced by damaged cells that die via either proinflammatory necroptosis or anti-inflammatory apoptosis. Both forms of cell death may be mediated by reactive oxygen species (ROS) generated during the proinflammatory response. Recent evidence suggests that exercise training boosts antioxidative capacity and could offer protection against sepsis. Given these findings, we aimed to examine the impact of exercise training on neural cell death in the context of sepsis. Methods: We assessed the effectiveness of exercise in reducing ROS production and the inflammatory response using a cecal ligation and puncture (CLP)-induced sepsis model. Forty C57BL/6N male mice were randomly divided into 2 groups: control (CLP-Con; n=20) and experimental (CLP-Ex; n=20). Before the induction of sepsis by CLP, the CLP-Ex mice underwent interval training on a treadmill 3 days per week for 8 weeks. Each day involved 10 cycles of 2 minutes at 8 m/min and 2 minutes at 15 m/min. After the CLP procedure, we monitored the survival of 10 mice from each group over a 30-hour period. Results: The findings indicated that exercise training increased the survival rate among mice with CLP-induced sepsis by enhancing antioxidative capacity and delaying the transition from a hyperdynamic to an immunosuppressive state. Conclusions: Exercise training may delay the progression from the hyperdynamic state to the hypodynamic phase of sepsis by increasing antioxidant capacity and reducing apoptotic cell death.
참고문헌 (35)
- Cao C, "Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis", Cell Death Dis, 10, pp.782~ (2019)
- Rudd KE, "Global, regional, and national sepsis incidence and mortality, 1990–2017 : analysis for the Global Burden of Disease Study", Lancet, 395, pp.200~211 (2020)
- Singer M, "The third international consensus definitions for sepsis and septic shock(Sepsis-3)", JAMA, 315, pp.801~810 (2016)
- Doi K, "Animal models of sepsis and sepsis-induced kidney injury", J Clin Invest, 119, pp.2868~2878 (2009)
- Hotchkiss RS, "Immunosuppression in sepsis : a novel understanding of the disorder and a new therapeutic approach", Lancet Infect Dis, 13, pp.260~268 (2013)
- Cho YS, "The role of necroptosis in the treatment of diseases", BMB Rep, 51, pp.219~224 (2018)
- Vanden Berghe T, "Molecular crosstalk between apoptosis, necroptosis, and survival signaling", Mol Cell Oncol, 2, pp.e975093~ (2015)
- Pasparakis M, "Necroptosis and its role in inflammation", Nature, 517, pp.311~320 (2015)
- Arazi H, "Creatine supplementation, physical exercise and oxidative stress markers : a review of the mechanisms and effectiveness", Nutrients, 13, pp.869~ (2021)
- Victor VM, "Role of free radicals in sepsis : antioxidant therapy", Curr Pharm Des, 11, pp.3141~3158 (2005)
- Thornton C, "Role of mitochondria in apoptotic and necroptotic cell death in the developing brain", Clin Chim Acta, 451, pp.35~38 (2015)
- Ono S, "Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis", Ann Gastroenterol Surg, 2, pp.351~358 (2018)
- Szondy Z, "Anti-inflammatory mechanisms triggered by apoptotic cells during their clearance", Front Immunol, 8, pp.909~ (2017)
- Danielski LG, "Brain barrier breakdown as a cause and consequence of neuroinflammation in sepsis", Mol Neurobiol, 55, pp.1045~1053 (2018)
- Semmler A, "Systemic inflammation induces apoptosis with variable vulnerability of different brain regions", J Chem Neuroanat, 30, pp.144~157 (2005)
- Dal-Pizzol F, "Oxidative mechanisms of brain dysfunction during sepsis", Neurochem Res, 35, pp.1~12 (2010)
- Mason SA, "Antioxidant supplements and endurance exercise : current evidence and mechanistic insights", Redox Biol, 35, pp.101471~ (2020)
- Margaritelis NV, "Antioxidant supplementation, redox deficiencies and exercise performance : a falsification design", Free Radic Biol Med, 158, pp.44~52 (2020)
- Osuru HP, "Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver", Critical Care, 27, pp.266~ (2023)
- de Araújo CC, "Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury", J Appl Physiol, 112, pp.1206~1214 (2012)
- Irahara T, "Lowintensity exercise in the acute phase of lipopolysaccharide-induced sepsis improves lipid metabolism and survival in mice by stimulating PGC-1α expression", J Trauma Acute Care Surg, 80, pp.933~940 (2016)
- Deng D, "Systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model and their characteristics", Int Immunopharmacol, 42, pp.49~58 (2017)
- Rittirsch D, "Immunodesign of experimental sepsis by cecal ligation and puncture", Nat Protoc, 4, pp.31~36 (2009)
- Sossdorf M, "Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis", Crit Care Med, 41, pp.e246~e255 (2013)
- Cardoso GH, "High-intensity exercise prevents disturbances in lung inflammatory cytokines and antioxidant defenses induced by lipopolysaccharide", Inflammation, 41, pp.2060~2067 (2018)
- Miron VV, "Physical exercise prevents alterations in purinergic system and oxidative status in lipopolysaccharide-induced sepsis in rats", J Cell Biochem, 120, pp.3232~3242 (2019)
- Coelho CW, "Exercise training prevents skeletal muscle damage in an experimental sepsis model", Clinics, 68, pp.107~114 (2013)
- Northington FJ, "Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI", J Cereb Blood Flow Metab, 31, pp.178~189 (2011)
- You Z, "Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice", J Cereb Blood Flow Metab, 28, pp.1564~1573 (2008)
- King MD, "Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage", Int J Cell Biol, 2014, pp.495817~ (2014)
- Ko YJ, "Voluntary wheel running improves spatial learning memory by suppressing inflammation and apoptosis via inactivation of nuclear factor kappa B in brain inflammation rats", Int Neurourol J, 24, pp.96~103 (2020)
- Song SH, "Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats", J Exerc Rehabil, 14, pp.911~919 (2018)
- Aboutaleb N, "Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax", Bcl-2proteins ratio and prevention of caspase-3 activation, 2015, pp.65, 435~443
- Cobley JN, "Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle", Longev Healthspan, 2, pp.11~ (2013)
- Mohamed JS, "Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism", Aging, 6, pp.820~834 (2014)