Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Perspective of Molecular Hydrogen in the Treatment of Sepsis

Author(s): Bo Qi, Yang Yu, Yaoqi Wang, Yuzun Wang, Yonghao Yu and Keliang Xie*

Volume 27, Issue 5, 2021

Published on: 09 September, 2020

Page: [667 - 678] Pages: 12

DOI: 10.2174/1381612826666200909124936

Price: $65

Abstract

Sepsis is the main cause of death in critically ill patients with no effective treatment. Sepsis is lifethreatening organ dysfunction due to a dysregulated host response to infection. As a novel medical gas, molecular hydrogen (H2) has a therapeutic effect on many diseases, such as sepsis. H2 treatment exerts multiple biological effects, which can effectively improve multiple organ injuries caused by sepsis. However, the underlying molecular mechanisms of hydrogen involved in the treatment of sepsis remain elusive, which are likely related to anti-inflammation, anti-oxidation, anti-apoptosis, regulation of autophagy and multiple signaling pathways. This review can help better understand the progress of hydrogen in the treatment of sepsis, and provide a theoretical basis for the clinical application of hydrogen therapy in sepsis in the future.

Keywords: Sepsis, molecular hydrogen, organ injury, inflammation, oxidative stress, mechanisms.

[1]
Singer M, Deutschman CS, Seymour CW, et al. The third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-10.
[http://dx.doi.org/10.1001/jama.2016.0287] [PMID: 26903338]
[2]
Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet 2018; 392(10141): 75-87.
[http://dx.doi.org/10.1016/S0140-6736(18)30696-2] [PMID: 29937192]
[3]
Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395(10219): 200-11.
[http://dx.doi.org/10.1016/S0140-6736(19)32989-7] [PMID: 31954465]
[4]
Fleischmann C, Scherag A, Adhikari NKJ, et al. International forum of acute care trialists. assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations. Am J Respir Crit Care Med 2016; 193(3): 259-72.
[http://dx.doi.org/10.1164/rccm.201504-0781OC] [PMID: 26414292]
[5]
Abe T, Ogura H, Shiraishi A, et al. JAAM FORECAST group. Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study. Crit Care 2018; 22(1): 322.
[http://dx.doi.org/10.1186/s13054-018-2186-7] [PMID: 30466493]
[6]
Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA 2014; 311(13): 1308-16.
[http://dx.doi.org/10.1001/jama.2014.2637] [PMID: 24638143]
[7]
Kennedy JL, Haberling DL, Huang CC, et al. Infectious disease hospitalizations: United States, 2001 to 2014. Chest 2019; 156(2): 255-68.
[http://dx.doi.org/10.1016/j.chest.2019.04.013] [PMID: 31047954]
[8]
van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol 2017; 17(7): 407-20.
[http://dx.doi.org/10.1038/nri.2017.36] [PMID: 28436424]
[9]
Li Y, Xie K, Chen H, Wang G, Yu Y. Hydrogen gas inhibits high-mobility group box 1 release in septic mice by upregulation of heme oxygenase 1. J Surg Res 2015; 196(1): 136-48.
[http://dx.doi.org/10.1016/j.jss.2015.02.042] [PMID: 25818978]
[10]
Yan M, Yu Y, Mao X, et al. Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner. Int Immunopharmacol 2019; 71: 61-7.
[http://dx.doi.org/10.1016/j.intimp.2019.03.021] [PMID: 30877875]
[11]
Chen H, Mao X, Meng X, et al. Hydrogen alleviates mitochondrial dysfunction and organ damage via autophagy-mediated NLRP3 inflammasome inactivation in sepsis. Int J Mol Med 2019; 44(4): 1309-24.
[http://dx.doi.org/10.3892/ijmm.2019.4311] [PMID: 31432098]
[12]
Li Y, Li Q, Chen H, et al. Hydrogen gas Alleviates the Intestinal Injury Caused by Severe Sepsis in Mice by Increasing the Expression of Heme Oxygenase-1. Shock 2015; 44(1): 90-8.
[http://dx.doi.org/10.1097/SHK.0000000000000382] [PMID: 25895145]
[13]
Liu L, Xie K, Chen H, et al. Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Res 2014; 1589: 78-92.
[http://dx.doi.org/10.1016/j.brainres.2014.09.030] [PMID: 25251596]
[14]
Xin Y, Liu H, Zhang P, Chang L, Xie K. Molecular hydrogen inhalation attenuates postoperative cognitive impairment in rats. Neuroreport 2017; 28(11): 694-700.
[http://dx.doi.org/10.1097/WNR.0000000000000824] [PMID: 28614179]
[15]
Huo TT, Zeng Y, Liu XN, et al. Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats. Anesth Analg 2014; 119(2): 368-80.
[http://dx.doi.org/10.1213/ANE.0000000000000303] [PMID: 24937348]
[16]
Zhou L, Wang X, Xue W, et al. Beneficial effects of hydrogen-rich saline against spinal cord ischemia-reperfusion injury in rabbits. Brain Res 2013; 1517: 150-60.
[http://dx.doi.org/10.1016/j.brainres.2013.04.007] [PMID: 23603405]
[17]
Mantzarlis K, Tsolaki V, Zakynthinos E. Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. Oxid Med Cell Longev 2017; 2017: 5985209.
[http://dx.doi.org/10.1155/2017/5985209] [PMID: 28904739]
[18]
Yu Y, Yang Y, Bian Y, et al. Hydrogen gas protects against intestinal injury in wild Type but not NRF2 knockout mice with severe sepsis by regulating HO-1 and HMGB1 release. Shock 2017; 48(3): 364-70.
[http://dx.doi.org/10.1097/SHK.0000000000000856] [PMID: 28234792]
[19]
Li Q, Jiao Y, Yu Y, Wang G, Yu Y. Hydrogen-rich medium alleviates high glucose-induced oxidative stress and parthanatos in rat Schwann cells in-vitro. Mol Med Rep 2019; 19(1): 338-44.
[PMID: 30431142]
[20]
Wang L, Zhao C, Wu S, et al. Hydrogen gas treatment improves the neurological outcome after traumatic brain injury via increasing miR-21 expression. Shock 2018; 50(3): 308-15.
[http://dx.doi.org/10.1097/SHK.0000000000001018] [PMID: 29028768]
[21]
Meng X, Chen H, Wang G, Yu Y, Xie K. Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. Exp Ther Med 2015; 10(6): 2277-82.
[http://dx.doi.org/10.3892/etm.2015.2787] [PMID: 26668628]
[22]
Liu H, Hua N, Xie K, Zhao T, Yu Y. Hydrogen-rich saline reduces cell death through inhibition of DNA oxidative stress and overactivation of poly (ADP-ribose) polymerase-1 in retinal ischemia-reperfusion injury. Mol Med Rep 2015; 12(2): 2495-502.
[http://dx.doi.org/10.3892/mmr.2015.3731] [PMID: 25954991]
[23]
Dong A, Yu Y, Wang Y, et al. Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics. Int Immunopharmacol 2018; 65: 366-72.
[http://dx.doi.org/10.1016/j.intimp.2018.10.012] [PMID: 30380511]
[24]
Xie K, Wang Y, Yin L, et al. Hydrogen gas alleviates sepsis-induced brain injury by improving mitochondrial biogenesis through the activation of PGC-alpha in mice SHOCK 2020; 55(1): 100-9.
[25]
Zhang Y, Dong A, Xie K, Yu Y. Protective effects of hydrogen on myocardial mitochondrial functions in septic mice. BioMed Res Int 2020; 2020: 1568209.
[http://dx.doi.org/10.1155/2020/1568209] [PMID: 32083123]
[26]
Jiao Y, Yu Y, Li B, et al. Protective effects of hydrogen-rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP-sensitive potassium channel channels in rats. Mol Med Rep 2020; 21(1): 282-90.
[PMID: 31746358]
[27]
Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003; 101(10): 3765-77.
[http://dx.doi.org/10.1182/blood-2002-06-1887] [PMID: 12543869]
[28]
Opal SM, van der Poll T. Endothelial barrier dysfunction in septic shock. J Intern Med 2015; 277(3): 277-93.
[http://dx.doi.org/10.1111/joim.12331] [PMID: 25418337]
[29]
Yu Y, Wang WN, Han HZ, Xie KL, Wang GL, Yu YH. Protective effects of hydrogen-rich medium on lipopolysaccharide-induced monocytic adhesion and vascular endothelial permeability through regulation of vascular endothelial cadherin. Genet Mol Res 2015; 14(2): 6202-12.
[http://dx.doi.org/10.4238/2015.June.9.6] [PMID: 26125821]
[30]
Crouser ED. Sepsis-induced endoplasmic reticulum stress: a matter of life and death? Crit Care Med 2016; 44(8): 1626-7.
[http://dx.doi.org/10.1097/CCM.0000000000001694] [PMID: 27428132]
[31]
Park SY, Shrestha S, Youn YJ, et al. Autophagy primes neutrophils for neutrophil extracellular trap formation during sepsis. Am J Respir Crit Care Med 2017; 196(5): 577-89.
[http://dx.doi.org/10.1164/rccm.201603-0596OC] [PMID: 28358992]
[32]
Chen H, Zhou C, Xie K, Meng X, Wang Y, Yu Y. Hydrogen-rich saline alleviated the hyperpathia and microglia activation via autophagy mediated inflammasome inactivation in neuropathic pain rats. Neuroscience 2019; 421: 17-30.
[http://dx.doi.org/10.1016/j.neuroscience.2019.10.046] [PMID: 31689487]
[33]
Zhao H, Chen H, Xiaoyin M, et al. Autophagy activation improves lung injury and inflammation in Sepsis. Inflammation 2019; 42(2): 426-39.
[http://dx.doi.org/10.1007/s10753-018-00952-5] [PMID: 30645707]
[34]
Ling H, Chen H, Wei M, Meng X, Yu Y, Xie K. The effect of autophagy on inflammation cytokines in renal ischemia/reperfusion injury. Inflammation 2016; 39(1): 347-56.
[http://dx.doi.org/10.1007/s10753-015-0255-5] [PMID: 26412257]
[35]
Nakada TA, Takahashi W, Nakada E, Shimada T, Russell JA, Walley KR. Genetic polymorphisms in Sepsis and Cardiovascular Disease: Do Similar Risk Genes Suggest Similar Drug Targets? Chest 2019; 155(6): 1260-71.
[http://dx.doi.org/10.1016/j.chest.2019.01.003] [PMID: 30660782]
[36]
ProCESS I. Yealy DM, Kellum JA,, et al. A randomized trial of protocol-based care for early septic shock. New Engl J Med 2014; 370(18): 1683-93.
[37]
Peake SL, Delaney A, Bailey M, et al. ARISE Investigators; ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371(16): 1496-506.
[http://dx.doi.org/10.1056/NEJMoa1404380] [PMID: 25272316]
[38]
Mouncey PR, Osborn TM, Power GS, et al. ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372(14): 1301-11.
[http://dx.doi.org/10.1056/NEJMoa1500896] [PMID: 25776532]
[39]
Bjurstedt H, Severin G. The prevention of decompression sickness and nitrogen narcosis by the use of hydrogen as a substitute for nitrogen, the Arne Zetterstrôm method for deep-sea diving. Mil Surg (Wash) 1948; 103(2): 107-16.
[http://dx.doi.org/10.1093/milmed/103.2.107] [PMID: 18876410]
[40]
Shirahata S, Kabayama S, Nakano M, et al. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochem Biophys Res Commun 1997; 234(1): 269-74.
[http://dx.doi.org/10.1006/bbrc.1997.6622] [PMID: 9169001]
[41]
Gharib B, Hanna S, Abdallahi OMS, Lepidi H, Gardette B, De Reggi M. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation. C R Acad Sci III 2001; 324(8): 719-24.
[http://dx.doi.org/10.1016/S0764-4469(01)01350-6] [PMID: 11510417]
[42]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[http://dx.doi.org/10.1038/nm1577] [PMID: 17486089]
[43]
Tao G, Song G, Qin S. Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases. Acta Biochim Biophys Sin (Shanghai) 2019; 51(12): 1189-97.
[http://dx.doi.org/10.1093/abbs/gmz121] [PMID: 31738389]
[44]
Li H, Chen O, Ye Z, et al. Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway. Biochem Pharmacol 2017; 130: 83-92.
[http://dx.doi.org/10.1016/j.bcp.2017.02.003] [PMID: 28188779]
[45]
Qiu X, Ye Q, Sun M, Wang L, Tan Y, Wu G. Saturated hydrogen improves lipid metabolism disorders and dysbacteriosis induced by a high-fat diet. Exp Biol Med (Maywood) 2020; 245(6): 512-21.
[http://dx.doi.org/10.1177/1535370219898407] [PMID: 31910652]
[46]
Saramago EA, Borges GS, Singolani-Jr CG, et al. Molecular hydrogen potentiates hypothermia and prevents hypotension and fever in LPS-induced systemic inflammation. Brain Behav Immun 2019; 75: 119-28.
[http://dx.doi.org/10.1016/j.bbi.2018.09.027] [PMID: 30261305]
[47]
Wang D, Wang L, Zhang Y, Zhao Y, Chen G. Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomed Pharmacother 2018; 104: 788-97.
[http://dx.doi.org/10.1016/j.biopha.2018.05.055] [PMID: 29852353]
[48]
Shao A, Wu H, Hong Y, et al. Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response: Possible involvement of NF-κB pathway and NLRP3 inflammasome. Mol Neurobiol 2016; 53(5): 3462-76.
[http://dx.doi.org/10.1007/s12035-015-9242-y] [PMID: 26091790]
[49]
Chen HG, Han HZ, Li Y, Yu YH, Xie KL. Hydrogen alleviated organ injury and dysfunction in sepsis: The role of cross-talk between autophagy and endoplasmic reticulum stress: Experimental research. Int Immunopharmacol 2020; 78: 106049.
[http://dx.doi.org/10.1016/j.intimp.2019.106049] [PMID: 31830624]
[50]
Xie K, Liu L, Yu Y, Wang G. Hydrogen gas presents a promising therapeutic strategy for sepsis. BioMed Res Int 2014; 2014: 807635.
[http://dx.doi.org/10.1155/2014/807635] [PMID: 24829918]
[51]
Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res 2011; 1(1): 24.
[http://dx.doi.org/10.1186/2045-9912-1-24] [PMID: 22146674]
[52]
Guan WJ, Wei CH, Chen AL, et al. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J Thorac Dis 2020; 12(6): 3448-52.
[http://dx.doi.org/10.21037/jtd-2020-057] [PMID: 32642277]
[53]
Chen JB, Kong XF, Mu F, Lu TY, Lu YY, Xu KC. Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer. Med Gas Res 2020; 10(2): 75-80.
[http://dx.doi.org/10.4103/2045-9912.285560] [PMID: 32541132]
[54]
Xie K, Yu Y, Pei Y, et al. Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Shock 2010; 34(1): 90-7.
[http://dx.doi.org/10.1097/SHK.0b013e3181cdc4ae] [PMID: 19997046]
[55]
Chen H, Xie K, Han H, et al. Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway. Int Immunopharmacol 2015; 28(1): 643-54.
[http://dx.doi.org/10.1016/j.intimp.2015.07.034] [PMID: 26253656]
[56]
Xie K, Wang W, Chen H, et al. Hydrogen-rich medium attenuated Lipopolysaccharide-induced monocyte-endothelial cell adhesion and vascular endothelial permeability via Rho-associated Coiled-Coil Protein Kinase. Shock 2015; 44(1): 58-64.
[http://dx.doi.org/10.1097/SHK.0000000000000365] [PMID: 25895142]
[57]
Liu L, Wu X, Tao B, Wang N, Zhang J. Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis. Genetics and molecular research. GMR 2016; 15(1): 10-4238.
[http://dx.doi.org/10.4238/gmr.15016050]
[58]
Tao B, Liu L, Wang N, Wang W, Jiang J, Zhang J. Effects of hydrogen-rich saline on aquaporin 1, 5 in septic rat lungs. J Surg Res 2016; 202(2): 291-8.
[http://dx.doi.org/10.1016/j.jss.2016.01.009] [PMID: 27229103]
[59]
Liu H, Liang X, Wang D, et al. Combination therapy with nitric oxide and molecular hydrogen in a murine model of acute lung injury. Shock 2015; 43(5): 504-11.
[http://dx.doi.org/10.1097/SHK.0000000000000316] [PMID: 25643010]
[60]
Hong Y, Sun LI, Sun R, Chen H, Yu Y, Xie K. Combination therapy of molecular hydrogen and hyperoxia improves survival rate and organ damage in a zymosan-induced generalized inflammation model. Exp Ther Med 2016; 11(6): 2590-6.
[http://dx.doi.org/10.3892/etm.2016.3231] [PMID: 27284352]
[61]
Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence 2014; 5(1): 36-44.
[http://dx.doi.org/10.4161/viru.25436] [PMID: 23774844]
[62]
Nedeva C, Menassa J, Puthalakath H. Sepsis: Inflammation is a necessary evil. Front Cell Dev Biol 2019; 7: 108.
[http://dx.doi.org/10.3389/fcell.2019.00108] [PMID: 31281814]
[63]
Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers 2016; 2: 16045.
[http://dx.doi.org/10.1038/nrdp.2016.45] [PMID: 28117397]
[64]
Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 2018; 233(9): 6425-40.
[http://dx.doi.org/10.1002/jcp.26429] [PMID: 29319160]
[65]
Yao W, Guo A, Han X, et al. Aerosol inhalation of a hydrogen-rich solution restored septic renal function. Aging (Albany NY) 2019; 11(24): 12097-113.
[http://dx.doi.org/10.18632/aging.102542] [PMID: 31841441]
[66]
Zhuang X, Yu Y, Jiang Y, et al. Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway. Int Immunopharmacol 2020; 81: 106287.
[http://dx.doi.org/10.1016/j.intimp.2020.106287] [PMID: 32058932]
[67]
Sakata H, Okamoto A, Aoyama-Ishikawa M, et al. Inhaled hydrogen ameliorates endotoxin-induced bowel dysfunction. Acute Med Surg 2016; 4(1): 38-45.
[http://dx.doi.org/10.1002/ams2.218] [PMID: 29123834]
[68]
Wang Y, Zhang J, Bo J, Wang X, Zhu J. Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice. Exp Biol Med (Maywood) 2019; 244(9): 721-7.
[http://dx.doi.org/10.1177/1535370219847941] [PMID: 31042074]
[69]
Andrades MÉ, Morina A, Spasić S, Spasojević I. Bench-to-bedside review: sepsis - from the redox point of view. Crit Care 2011; 15(5): 230.
[http://dx.doi.org/10.1186/cc10334] [PMID: 21996422]
[70]
Holzerová E, Prokisch H. Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production? Int J Biochem Cell Biol 2015; 63: 16-20.
[http://dx.doi.org/10.1016/j.biocel.2015.01.021] [PMID: 25666559]
[71]
Qiu P, Liu Y, Zhang J. Recent advances in studies of molecular hydrogen against sepsis. Int J Biol Sci 2019; 15(6): 1261-75.
[http://dx.doi.org/10.7150/ijbs.30741] [PMID: 31223285]
[72]
Nakano T, Kotani T, Mano Y, et al. Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury. J Clin Biochem Nutr 2015; 57(3): 178-82.
[http://dx.doi.org/10.3164/jcbn.15-90] [PMID: 26566302]
[73]
Hattori Y, Kotani T, Tsuda H, et al. Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. Free Radic Res 2015; 49(8): 1026-37.
[http://dx.doi.org/10.3109/10715762.2015.1038257] [PMID: 25947958]
[74]
Imai K, Kotani T, Tsuda H, et al. Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia. Free Radic Biol Med 2016; 91: 154-63.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.015] [PMID: 26709014]
[75]
Xin HG, Zhang BB, Wu ZQ, et al. Consumption of hydrogen-rich water alleviates renal injury in spontaneous hypertensive rats. Mol Cell Biochem 2014; 392(1-2): 117-24.
[http://dx.doi.org/10.1007/s11010-014-2024-4] [PMID: 24652103]
[76]
Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 2016; 8(4): 603-19.
[http://dx.doi.org/10.18632/aging.100934] [PMID: 27019364]
[77]
Tower J. Programmed cell death in aging. Ageing Res Rev 2015; 23(Pt A): 90-100.
[http://dx.doi.org/10.1016/j.arr.2015.04.002] [PMID: 25862945]
[78]
Girardot T, Rimmelé T, Venet F, Monneret G. Apoptosis-induced lymphopenia in sepsis and other severe injuries. Apoptosis 2017; 22(2): 295-305.
[http://dx.doi.org/10.1007/s10495-016-1325-3] [PMID: 27812767]
[79]
Hattori Y, Hattori K, Suzuki T, Matsuda N. Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges. Pharmacol Ther 2017; 177: 56-66.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.040] [PMID: 28232275]
[80]
Zhang Y, Liu Y, Zhang J. Saturated hydrogen saline attenuates endotoxin-induced lung dysfunction. J Surg Res 2015; 198(1): 41-9.
[http://dx.doi.org/10.1016/j.jss.2015.04.055] [PMID: 26004495]
[81]
Fu Z, Zhang Z, Wu X, Zhang J. Hydrogen-rich saline inhibits Lipopolysaccharide-induced acute lung injury and endothelial dysfunction by regulating autophagy through mTOR/TFEB signaling pathway. BioMed Res Int 2020; 2020: 9121894.
[http://dx.doi.org/10.1155/2020/9121894] [PMID: 32071922]
[82]
Shibutani ST, Saitoh T, Nowag H, Münz C, Yoshimori T. Autophagy and autophagy-related proteins in the immune system. Nat Immunol 2015; 16(10): 1014-24.
[http://dx.doi.org/10.1038/ni.3273] [PMID: 26382870]
[83]
Ho J, Yu J, Wong SH, et al. Autophagy in sepsis: Degradation into exhaustion? Autophagy 2016; 12(7): 1073-82.
[http://dx.doi.org/10.1080/15548627.2016.1179410] [PMID: 27172163]
[84]
Deretic V, Levine B. Autophagy balances inflammation in innate immunity. Autophagy 2018; 14(2): 243-51.
[http://dx.doi.org/10.1080/15548627.2017.1402992] [PMID: 29165043]
[85]
Sun Y, Cai Y, Zang QS. Cardiac autophagy in sepsis. Cells 2019; 8(2): 141.
[http://dx.doi.org/10.3390/cells8020141] [PMID: 30744190]
[86]
Sun Y, Yao X, Zhang QJ, et al. Beclin-1-dependent autophagy protects the heart during sepsis. Circulation 2018; 138(20): 2247-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032821] [PMID: 29853517]
[87]
Cha-Molstad H, Yu JE, Feng Z, et al. p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis. Nat Commun 2017; 8(1): 102.
[http://dx.doi.org/10.1038/s41467-017-00085-7] [PMID: 28740232]
[88]
Yu Y, Yang Y, Yang M, Wang C, Xie K, Yu Y. Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway. Int Immunopharmacol 2019; 69: 11-8.
[http://dx.doi.org/10.1016/j.intimp.2019.01.022] [PMID: 30660872]
[89]
Yu Y, Feng J, Lian N, et al. Hydrogen gas alleviates blood-brain barrier impairment and cognitive dysfunction of septic mice in an Nrf2-dependent pathway. Int Immunopharmacol 2020; 85: 106585.
[http://dx.doi.org/10.1016/j.intimp.2020.106585] [PMID: 32447221]
[90]
Zhang B, Zhao Z, Meng X, Chen H, Fu G, Xie K. Hydrogen ameliorates oxidative stress via PI3K-Akt signaling pathway in UVB-induced HaCaT cells. Int J Mol Med 2018; 41(6): 3653-61.
[http://dx.doi.org/10.3892/ijmm.2018.3550] [PMID: 29532858]
[91]
Chen Y, Chen H, Xie K, et al. H2 treatment attenuated pain behavior and cytokine release through the HO-1/CO pathway in a rat model of neuropathic pain. Inflammation 2015; 38(5): 1835-46.
[http://dx.doi.org/10.1007/s10753-015-0161-x] [PMID: 25820467]
[92]
Chen HG, Xie KL, Han HZ, et al. Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages. Int J Surg 2013; 11(10): 1060-6.
[http://dx.doi.org/10.1016/j.ijsu.2013.10.007] [PMID: 24148794]
[93]
Yang HM, Yang S, Huang SS, Tang BS, Guo JF. Microglial activation in the pathogenesis of Huntington’s disease. Front Aging Neurosci 2017; 9: 193.
[http://dx.doi.org/10.3389/fnagi.2017.00193] [PMID: 28674491]
[94]
Dadon-Freiberg M, Chapnik N, Froy O. REV-ERBalpha activates the mTOR signalling pathway and promotes myotubes differentiation. Biol Cell 2020; 112(8): 213-21.
[95]
Papadopoli D, Boulay K, Kazak L, et al. mTOR as a central regulator of lifespan and aging. F1000Res 2019; 8: F1000 Faculty Rev-998.
[96]
Park SY, Koh HC. FUNDC1 regulates receptor-mediated mitophagy independently of the PINK1/Parkin-dependent pathway in rotenone-treated SH-SY5Y cells. Food Chem Toxicol 2020; 137: 111163.
[http://dx.doi.org/10.1016/j.fct.2020.111163] [PMID: 32001317]
[97]
Lampert MA, Orogo AM, Najor RH, et al. BNIP3L/NIX and FUNDC1-mediated mitophagy is required for mitochondrial network remodeling during cardiac progenitor cell differentiation. Autophagy 2019; 15(7): 1182-98.
[http://dx.doi.org/10.1080/15548627.2019.1580095] [PMID: 30741592]
[98]
Lv M, Wang C, Li F, et al. Structural insights into the recognition of phosphorylated FUNDC1 by LC3B in mitophagy. Protein Cell 2017; 8(1): 25-38.
[http://dx.doi.org/10.1007/s13238-016-0328-8] [PMID: 27757847]
[99]
Yao L, Chen H, Wu Q, Xie K. Hydrogen-rich saline alleviates inflammation and apoptosis in myocardial I/R injury via PINK-mediated autophagy. Int J Mol Med 2019; 44(3): 1048-62.
[http://dx.doi.org/10.3892/ijmm.2019.4264] [PMID: 31524220]
[100]
Li Y, Chen H, Shu R, et al. Hydrogen treatment prevents lipopolysaccharide-induced pulmonary endothelial cell dysfunction through RhoA inhibition. Biochem Biophys Res Commun 2020; 522(2): 499-505.
[http://dx.doi.org/10.1016/j.bbrc.2019.11.101] [PMID: 31780264]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy