{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:14:46Z","timestamp":1780762486590,"version":"3.54.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Chronic inflammation and oxidative stress are major triggers of the imbalance between protein synthesis and degradation during the pathogenesis of immobilization-induced muscle atrophy. This study aimed to elucidate the effects of hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), a gas transmitter with potent anti-inflammatory and antioxidant properties, on immobilization-induced muscle atrophy. Mice were allocated to control and immobilization (IM) groups, which were treated with slow (GYY4137) or rapid (NaHS) H<jats:sub>2<\/jats:sub>S releasing donors for 14\u00a0days. The results showed that both GYY4137 and NaHS treatment reduced the IM-induced muscle loss, and increased muscle mass. The IM-induced expressions of Muscle RING finger 1 (MuRF1) and atrogin-1, two muscle-specific E3 ubiquitin ligases, were decreased by administration of GYY4137 or NaHS. Both GYY4137 and NaHS treatments alleviated the IM-induced muscle fibrosis, as evidenced by decreases in collagen deposition and levels of tissue fibrosis biomarkers. Moreover, administration of GYY4137 or NaHS alleviated the IM-induced infiltration of CD45 <jats:sup>+<\/jats:sup> leukocytes, meanwhile inhibited the expressions of the pro-inflammatory biomarkers in skeletal muscles. It was found that administration of either GYY4137 or NaHS significantly attenuated immobilization-induced oxidative stress as indicated by decreased H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> levels and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) immunoreactivity, as well as increased total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (NRF2) and NRF2 downstream anti-oxidant targets levels in skeletal muscles. Collectively, the present study demonstrated that treatment with either slow or rapid H<jats:sub>2<\/jats:sub>S releasing donors protected mice against immobilization-induced muscle fibrosis and atrophy. The beneficial effects of H<jats:sub>2<\/jats:sub>S on immobilization-induced skeletal muscle atrophy might be due to both the anti-inflammatory and anti-oxidant properties of H<jats:sub>2<\/jats:sub>S.<\/jats:p>","DOI":"10.3389\/fphys.2022.844539","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:03:22Z","timestamp":1649225002000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["H2S Protects Against Immobilization-Induced Muscle Atrophy via Reducing Oxidative Stress and Inflammation"],"prefix":"10.3389","volume":"13","author":[{"given":"Miaomiao","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Jian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","first-page":"197","article-title":"Effects of High-Intensity Training on Prostate Cancer-Induced Cardiac Atrophy","volume":"13","author":"Baumfalk","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.ejphar.2012.11.025","article-title":"Hydrogen Sulfide Inhibits Oxidative Stress in Lungs from Allergic Mice In Vivo","volume":"698","author":"Benetti","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"L896","DOI":"10.1152\/ajplung.00053.2006","article-title":"Role of Substance P in Hydrogen Sulfide-Induced Pulmonary Inflammation in Mice","volume":"291","author":"Bhatia","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/6825452","article-title":"Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology","volume":"2018","author":"Bitar","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1242\/dmm.010389","article-title":"Cellular and Molecular Mechanisms of Muscle Atrophy","volume":"6","author":"Bonaldo","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"B6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/1471-2474-12-185","article-title":"The Proteasome Inhibitor MG132 Reduces Immobilization-Induced Skeletal Muscle Atrophy in Mice","volume":"12","author":"Caron","year":"2011","journal-title":"BMC Musculoskelet. Disord."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/3206982","article-title":"Gasotransmitters: Potential Therapeutic Molecules of Fibrotic Diseases","volume":"2021","author":"Chen","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nrd4467","article-title":"Muscle Wasting in Disease: Molecular Mechanisms and Promising Therapies","volume":"14","author":"Cohen","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"B9","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1161\/01.RES.0000187457.24338.3D","article-title":"NAD(P)H Oxidase 4 Mediates Transforming Growth Factor-\u03b21-Induced Differentiation of Cardiac Fibroblasts into Myofibroblasts","volume":"97","author":"Cucoranu","year":"2005","journal-title":"Circ. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1158\/1535-7163.MCT-15-0691-T","article-title":"A Fast Hydrogen Sulfide-Releasing Donor Increases the Tumor Response to Radiotherapy","volume":"15","author":"De Preter","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jss.2018.08.048","article-title":"Hydrogen Sulfide Donor GYY4137 Acts through Endothelial Nitric Oxide to Protect Intestine in Murine Models of Necrotizing Enterocolitis and Intestinal Ischemia","volume":"234","author":"Drucker","year":"2019","journal-title":"J. Surg. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e13177","DOI":"10.1111\/apha.13177","article-title":"Exercise Training Ameliorates Bleomycin-Induced Epithelial Mesenchymal Transition and Lung Fibrosis through Restoration of H2 S Synthesis","volume":"225","author":"Du","year":"2019","journal-title":"Acta Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bone.2015.04.016","article-title":"Osteoporosis and Sarcopenia in Older Age","volume":"80","author":"Edwards","year":"2015","journal-title":"Bone"},{"key":"B14","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/mus.20399","article-title":"A Model of Muscle Atrophy Using Cast Immobilization in Mice","volume":"32","author":"Frimel","year":"2005","journal-title":"Muscle Nerve"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4777","DOI":"10.3390\/ijms21134777","article-title":"NRF2, a Transcription Factor for Stress Response and beyond","volume":"21","author":"He","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/mus.24558","article-title":"Upregulation of Interleukin-1\u03b2\/transforming Growth Factor-\u03b21 and Hypoxia Relate to Molecular Mechanisms Underlying Immobilization-Induced Muscle Contracture","volume":"52","author":"Honda","year":"2015","journal-title":"Muscle Nerve"},{"key":"B17","doi-asserted-by":"publisher","first-page":"677110","DOI":"10.3389\/fphar.2021.677110","article-title":"Endogenous Hydrogen Sulfide Is an Important Factor in Maintaining Arterial Oxygen Saturation","volume":"12","author":"Huang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1111\/cts.13081","article-title":"Hydrogen Sulfide Donor Protects against Mechanical Ventilation\u2010induced Atrophy and Contractile Dysfunction in the Rat Diaphragm","volume":"14","author":"Ichinoseki\u2010Sekine","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/mus.20442","article-title":"Intracellular Signaling during Skeletal Muscle Atrophy","volume":"33","author":"Kandarian","year":"2006","journal-title":"Muscle Nerve"},{"key":"B20","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/jcsm.12297","article-title":"Aspiration Pneumonia Induces Muscle Atrophy in the Respiratory, Skeletal, and Swallowing Systems","volume":"9","author":"Komatsu","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.niox.2019.05.008","article-title":"Hydrogen Sulfide Suppresses Homocysteine-Induced Glial Activation and Inflammatory Response","volume":"90","author":"Kumar","year":"2019","journal-title":"Nitric Oxide"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0143600","DOI":"10.1371\/journal.pone.0143600","article-title":"Pyrroloquinoline Quinone Resists Denervation-Induced Skeletal Muscle Atrophy by Activating PGC-1\u03b1 and Integrating Mitochondrial Electron Transport Chain Complexes","volume":"10","author":"Kuo","year":"2015","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.freeradbiomed.2009.04.014","article-title":"GYY4137, a Novel Hydrogen Sulfide-Releasing Molecule, Protects against Endotoxic Shock in the Rat","volume":"47","author":"Li","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/jcmm.12016","article-title":"The Complex Effects of the Slow-Releasing Hydrogen Sulfide Donor GYY4137 in a Model of Acute Joint Inflammation and in Human Cartilage Cells","volume":"17","author":"Li","year":"2013","journal-title":"J. Cel. Mol. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/9925771","article-title":"Hydrogen Sulfide Attenuates Angiotensin II-Induced Cardiac Fibroblast Proliferation and Transverse Aortic Constriction-Induced Myocardial Fibrosis through Oxidative Stress Inhibition via Sirtuin 3","volume":"2021","author":"Liu","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"9362","DOI":"10.1111\/jcmm.15587","article-title":"Hydrogen Sulphide Ameliorating Skeletal Muscle Atrophy in Db\/db Mice via Muscle RING finger 1 S\u2010sulfhydration","volume":"24","author":"Lu","year":"2020","journal-title":"J. Cel Mol. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s12576-016-0492-x","article-title":"Astaxanthin Supplementation Attenuates Immobilization-Induced Skeletal Muscle Fibrosis via Suppression of Oxidative Stress","volume":"67","author":"Maezawa","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"C609","DOI":"10.1152\/ajpcell.00147.2018","article-title":"Hydrogen Sulfide Alleviates Hyperhomocysteinemia-Mediated Skeletal Muscle Atrophy via Mitigation of Oxidative and Endoplasmic Reticulum Stress Injury","volume":"315","author":"Majumder","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.3390\/ijms11041509","article-title":"Oxidative Stress, Molecular Inflammation and Sarcopenia","volume":"11","author":"Meng","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/mus.20743","article-title":"Oxidative Stress, Chronic Disease, and Muscle Wasting","volume":"35","author":"Moylan","year":"2007","journal-title":"Muscle Nerve"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1113\/jphysiol.2010.203232","article-title":"Redox Homeostasis, Oxidative Stress and Disuse Muscle Atrophy","volume":"589","author":"Pellegrino","year":"2011","journal-title":"J. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/s0092-8674(04)00400-3","article-title":"Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy","volume":"117","author":"Sandri","year":"2004","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"H1164","DOI":"10.1152\/ajpheart.00831.2015","article-title":"Tumor Necrosis Factor-\u03b1 Impairs Adiponectin Signalling, Mitochondrial Biogenesis, and Myogenesis in Primary Human Myotubes Cultures","volume":"310","author":"Sente","year":"2016","journal-title":"Am. J. Physiol. Heart Circulatory Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"29011","DOI":"10.1074\/jbc.M601545200","article-title":"Global Translational Responses to Oxidative Stress Impact upon Multiple Levels of Protein Synthesis","volume":"281","author":"Shenton","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"722","DOI":"10.3390\/biom10050722","article-title":"The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice","volume":"10","author":"Smink","year":"2020","journal-title":"Biomolecules"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1080\/15548627.2017.1328348","article-title":"Azithromycin Attenuates Myofibroblast Differentiation and Lung Fibrosis Development through Proteasomal Degradation of NOX4","volume":"13","author":"Tsubouchi","year":"2017","journal-title":"Autophagy"},{"key":"B37","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.arr.2013.07.003","article-title":"Skeletal Muscle Atrophy during Short-Term Disuse: Implications for Age-Related Sarcopenia","volume":"12","author":"Wall","year":"","journal-title":"Ageing Res. Rev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4872","DOI":"10.1210\/jc.2013-2098","article-title":"Disuse Impairs the Muscle Protein Synthetic Response to Protein Ingestion in Healthy Men","volume":"98","author":"Wall","year":"","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1089\/ars.2009.2899","article-title":"The Effect of Hydrogen Sulfide Donors on Lipopolysaccharide-Induced Formation of Inflammatory Mediators in Macrophages","volume":"12","author":"Whiteman","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1089\/ars.2012.4645","article-title":"Hydrogen Sulfide Protects against Cellular Senescence via S-Sulfhydration of Keap1 and Activation of Nrf2","volume":"18","author":"Yang","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1242\/dmm.019414","article-title":"The Role of mTOR Signaling in the Regulation of Protein Synthesis and Muscle Mass during Immobilization in Mice","volume":"8","author":"You","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"B42","doi-asserted-by":"publisher","first-page":"L1193","DOI":"10.1152\/ajplung.00489.2005","article-title":"Role of Hydrogen Sulfide in Cecal Ligation and Puncture-Induced Sepsis in the Mouse","volume":"290","author":"Zhang","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e21511","DOI":"10.1096\/fj.202002675R","article-title":"Cystathionine Gamma\u2010lyase\/H 2 S Signaling Facilitates Myogenesis under Aging and Injury Condition","volume":"35","author":"Zhang","year":"2021","journal-title":"FASEB J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"533690","DOI":"10.3389\/fphys.2020.533690","article-title":"Hydrogen Sulfide Alleviates Skeletal Muscle Fibrosis via Attenuating Inflammation and Oxidative Stress","volume":"11","author":"Zhao L","year":"2020","journal-title":"Front. Physiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"571810","DOI":"10.3389\/fphys.2020.571810","article-title":"Reactive Oxygen Species Interact with NLRP3 Inflammasomes and Are Involved in the Inflammation of Sepsis: From Mechanism to Treatment of Progression","volume":"11","author":"Zhao S","year":"2020","journal-title":"Front. Physiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"111779","DOI":"10.1016\/j.yexcr.2019.111779","article-title":"H2S Alleviates Renal Injury and Fibrosis in Response to Unilateral Ureteral Obstruction by Regulating Macrophage Infiltration via Inhibition of NLRP3 Signaling","volume":"387","author":"Zhou","year":"2020","journal-title":"Exp. Cel Res."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.844539\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:03:25Z","timestamp":1649225005000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.844539\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":46,"alternative-id":["10.3389\/fphys.2022.844539"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.844539","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]},"article-number":"844539"}}