Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

Molecular Hydrogen Promotes Adipose-derived Stem Cell Myogenic Differentiation via Regulation of Mitochondria

Author(s): Yu-Xia Yang, Wen-Yong Fei*, Ming-Sheng Liu, Yu-Cheng Zhang, Rang-Shan Gao, Yang-Yang Hu, Er-Kai Pang and Lei Hou

Volume 18, Issue 6, 2023

Published on: 25 October, 2022

Page: [864 - 875] Pages: 12

DOI: 10.2174/1574888X17666220926115240

Price: $65

Abstract

Background: Acute skeletal muscle injuries are common physical or sports traumas. Cellular therapy has excellent potential for regeneration after skeletal muscle injury. Adipose-derived stem cells (ADSCs) are a more accessible type of stem cell. However, it has a low survival rate and differentiation efficiency in the oxidative stress-rich microenvironment after transplantation. Although molecular hydrogen (H2) possesses anti-inflammatory and antioxidant biological properties, its utility in mitochondrial and stem cell research has not been adequately explored.

Objective: This study aimed to reveal the role of H2 on adipose-derived stem cells' myogenic differentiation.

Methods: The protective effects of H2 in ADSCs were evaluated by MTT assay, live-dead cell staining, western blot analysis, immunofluorescence staining, confocal imaging, and transmission electron microscopy.

Results: An appropriate volume fraction of H2 significantly decreased mitochondrial reactive oxygen species (ROS) levels, increased the number of mitochondria, and promoted mitophagy, thus enhancing the survival and myogenic differentiation of ADSCs.

Conclusion: This study reveals the application potential of H2 in skeletal muscle diseases or other pathologies related to mitochondrial dysfunction.

Keywords: Molecular hydrogen, mitophagy, adipose-derived stem cells, myogenic differentiation, reactive oxygen species, cellular therapy

« Previous
Graphical Abstract

[1]
Wong S, Ning A, Lee C, Feeley BT. Return to sport after muscle injury. Curr Rev Musculoskelet Med 2015; 8(2): 168-75.
[http://dx.doi.org/10.1007/s12178-015-9262-2] [PMID: 25742905]
[2]
Ekstrand J, Hägglund M, Waldén M. Epidemiology of muscle injuries in professional football (soccer). Am J Sports Med 2011; 39(6): 1226-32.
[http://dx.doi.org/10.1177/0363546510395879] [PMID: 21335353]
[3]
Buckingham M, Montarras D. Skeletal muscle stem cells. Curr Opin Genet Dev 2008; 18(4): 330-6.
[http://dx.doi.org/10.1016/j.gde.2008.06.005] [PMID: 18625314]
[4]
Smith C, Kruger MJ, Smith RM, Myburgh KH. The inflammatory response to skeletal muscle injury: Illuminating complexities. Sports Med 2008; 38(11): 947-69.
[http://dx.doi.org/10.2165/00007256-200838110-00005] [PMID: 18937524]
[5]
Liu J, Saul D, Böker KO, Ernst J, Lehman W, Schilling AF. Current methods for skeletal muscle tissue repair and regeneration. BioMed Res Int 2018; 2018: 1984879.
[http://dx.doi.org/10.1155/2018/1984879] [PMID: 29850487]
[6]
Gharaibeh B, Chun LY, Hagen T, et al. Biological approaches to improve skeletal muscle healing after injury and disease. Birth Defects Res C Embryo Today 2012; 96(1): 82-94.
[http://dx.doi.org/10.1002/bdrc.21005] [PMID: 22457179]
[7]
Altamirano DE, Noller K, Mihaly E, Grayson WL. Recent advances toward understanding the role of transplanted stem cells in tissue-engineered regeneration of musculoskeletal tissues. F1000 Res 2020; 9: 118.
[http://dx.doi.org/10.12688/f1000research.21333.1] [PMID: 32117568]
[8]
Judson RN, Rossi FMV. Towards stem cell therapies for skeletal muscle repair. NPJ Regen Med 2020; 5(1): 10.
[http://dx.doi.org/10.1038/s41536-020-0094-3] [PMID: 32411395]
[9]
Qazi TH, Duda GN, Ort MJ, Perka C, Geissler S, Winkler T. Cell therapy to improve regeneration of skeletal muscle injuries. J Cachexia Sarcopenia Muscle 2019; 10(3): 501-16.
[http://dx.doi.org/10.1002/jcsm.12416] [PMID: 30843380]
[10]
McCullagh KJA, Perlingeiro RCR. Coaxing stem cells for skeletal muscle repair. Adv Drug Deliv Rev 2015; 84: 198-207.
[http://dx.doi.org/10.1016/j.addr.2014.07.007] [PMID: 25049085]
[11]
Passipieri JA, Christ GJ. The potential of combination therapeutics for more complete repair of volumetric muscle loss injuries: The role of exogenous growth factors and/or progenitor cells in implantable skeletal muscle tissue engineering technologies. Cells Tissues Organs 2016; 202(3-4): 202-13.
[http://dx.doi.org/10.1159/000447323] [PMID: 27825153]
[12]
Elahi KC, Klein G, Avci AM, Sievert KD, MacNeil S, Aicher WK. Human mesenchymal stromal cells from different sources diverge in their expression of cell surface proteins and display distinct differentiation patterns. Stem Cells Int 2016; 2016: 5646384.
[http://dx.doi.org/10.1155/2016/5646384] [PMID: 26770208]
[13]
Negroni E, Riederer I, Chaouch S, et al. In vivo myogenic potential of human CD133+ muscle-derived stem cells: A quantitative study. Mol Ther 2009; 17(10): 1771-8.
[http://dx.doi.org/10.1038/mt.2009.167] [PMID: 19623164]
[14]
Webster MT, Manor U, Lippincott SJ, Fan CM. Intravital imaging reveals ghost fibers as architectural units guiding myogenic progenitors during regeneration. Cell Stem Cell 2016; 18(2): 243-52.
[http://dx.doi.org/10.1016/j.stem.2015.11.005] [PMID: 26686466]
[15]
Si Z, Wang X, Sun C, et al. Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed Pharmacother 2019; 114: 108765.
[http://dx.doi.org/10.1016/j.biopha.2019.108765] [PMID: 30921703]
[16]
Kostyuk SV, Proskurnina EV, Ershova ES, et al. The phosphonate derivative of C60 fullerene induces differentiation towards the myogenic lineage in human adipose-derived mesenchymal stem cells. Int J Mol Sci 2021; 22(17): 9284.
[http://dx.doi.org/10.3390/ijms22179284] [PMID: 34502190]
[17]
Sung SE, Hwang M, Kim AY, et al. MyoD overexpressed equine adipose-derived stem cells enhanced myogenic differentiation potential. Cell Transplant 2016; 25(11): 2017-26.
[http://dx.doi.org/10.3727/096368916X691015] [PMID: 26892394]
[18]
Mizuno H, Zuk PA, Zhu M, Lorenz PH, Benhaim P, Hedrick MH. Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg 2002; 109(1): 199-209.
[http://dx.doi.org/10.1097/00006534-200201000-00030] [PMID: 11786812]
[19]
Forcales SV. Potential of adipose-derived stem cells in muscular regenerative therapies. Front Aging Neurosci 2015; 7: 123.
[http://dx.doi.org/10.3389/fnagi.2015.00123] [PMID: 26217219]
[20]
Bhattacharya D, Scimè A. Mitochondrial function in muscle stem cell fates. Front Cell Dev Biol 2020; 8: 480.
[http://dx.doi.org/10.3389/fcell.2020.00480] [PMID: 32612995]
[21]
Xu X, Duan S, Yi F, Ocampo A, Liu GH, Izpisua BJC. Mitochondrial regulation in pluripotent stem cells. Cell Metab 2013; 18(3): 325-32.
[http://dx.doi.org/10.1016/j.cmet.2013.06.005] [PMID: 23850316]
[22]
Peker N, Donipadi V, Sharma M, McFarlane C, Kambadur R. Loss of Parkin impairs mitochondrial function and leads to muscle atrophy. Am J Physiol Cell Physiol 2018; 315(2): C164-85.
[http://dx.doi.org/10.1152/ajpcell.00064.2017] [PMID: 29561660]
[23]
Sung YJ, Kao TY, Kuo CL, et al. Mitochondrial lon sequesters and stabilizes p53 in the matrix to restrain apoptosis under oxidative stress via its chaperone activity. Cell Death Dis 2018; 9(6): 697.
[http://dx.doi.org/10.1038/s41419-018-0730-7] [PMID: 29899330]
[24]
Dan DJ, Alvarez LAJ, Zhang X, Soldati T. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis. Redox Biol 2015; 6: 472-85.
[http://dx.doi.org/10.1016/j.redox.2015.09.005] [PMID: 26432659]
[25]
Vincow ES, Merrihew G, Thomas RE, et al. The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci USA 2013; 110(16): 6400-5.
[http://dx.doi.org/10.1073/pnas.1221132110] [PMID: 23509287]
[26]
Eiyama A, Okamoto K. PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol 2015; 33: 95-101.
[http://dx.doi.org/10.1016/j.ceb.2015.01.002] [PMID: 25697963]
[27]
Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183(5): 795-803.
[http://dx.doi.org/10.1083/jcb.200809125] [PMID: 19029340]
[28]
Manzella N, Santin Y, Maggiorani D, et al. Monoamine oxidase-A is a novel driver of stress-induced premature senescence through inhibition of parkin-mediated mitophagy. Aging Cell 2018; 17(5): e12811.
[http://dx.doi.org/10.1111/acel.12811] [PMID: 30003648]
[29]
Zhang F, Peng W, Zhang J, et al. P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head. Cell Death Dis 2020; 11(1): 42.
[http://dx.doi.org/10.1038/s41419-020-2238-1] [PMID: 31959744]
[30]
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]
[31]
Alwazeer D, Liu FFC, Wu XY, LeBaron TW. Combating oxidative stress and inflammation in covid-19 by molecular hydrogen therapy: Mechanisms and perspectives. Oxid Med Cell Longev 2021; 2021: 5513868.
[http://dx.doi.org/10.1155/2021/5513868] [PMID: 34646423]
[32]
Yang M, Dong Y, He Q, et al. Hydrogen: A novel option in human disease treatment. Oxid Med Cell Longev 2020; 2020: 8384742.
[http://dx.doi.org/10.1155/2020/8384742] [PMID: 32963703]
[33]
Watanabe M, Kamimura N, Iuchi K, et al. Protective effect of hydrogen gas inhalation on muscular damage using a mouse hindlimb ischemia-reperfusion injury model. Plast Reconstr Surg 2017; 140(6): 1195-206.
[http://dx.doi.org/10.1097/PRS.0000000000003878] [PMID: 30998612]
[34]
Hasegawa S, Ito M, Fukami M, Hashimoto M, Hirayama M, Ohno K. Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice. Redox Rep 2017; 22(1): 26-34.
[http://dx.doi.org/10.1080/13510002.2015.1135580] [PMID: 26866650]
[35]
Nie C, Zou R, Pan S, et al. Hydrogen gas inhalation ameliorates cardiac remodelling and fibrosis by regulating NLRP3 inflammasome in myocardial infarction rats. J Cell Mol Med 2021; 25(18): 8997-9010.
[http://dx.doi.org/10.1111/jcmm.16863] [PMID: 34402164]
[36]
Murakami Y, Ito M, Ohsawa I. Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis. PLoS One 2017; 12(5): e0176992.
[http://dx.doi.org/10.1371/journal.pone.0176992] [PMID: 28467497]
[37]
Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H 2 therapy in Parkinson’s disease: A randomized double-blind placebo-controlled trial. Mov Disord 2013; 28(6): 836-9.
[http://dx.doi.org/10.1002/mds.25375] [PMID: 23400965]
[38]
Ishihara G, Kawamoto K, Komori N, Ishibashi T. Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential. Biochem Biophys Res Commun 2020; 522(4): 965-70.
[http://dx.doi.org/10.1016/j.bbrc.2019.11.135] [PMID: 31810604]
[39]
Jensen EC. Quantitative analysis of histological staining and fluorescence using imageJ. Anat Rec 2013; 296(3): 378-81.
[http://dx.doi.org/10.1002/ar.22641] [PMID: 23382140]
[40]
Menconi M, Gonnella P, Petkova V, Lecker S, Hasselgren PO. Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes. J Cell Biochem 2008; 105(2): 353-64.
[http://dx.doi.org/10.1002/jcb.21833] [PMID: 18615595]
[41]
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - Current trends and future prospective. Biosci Rep 2015; 35(2): e00191.
[http://dx.doi.org/10.1042/BSR20150025] [PMID: 25797907]
[42]
Zannettino ACW, Paton S, Arthur A, et al. Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol 2008; 214(2): 413-21.
[http://dx.doi.org/10.1002/jcp.21210] [PMID: 17654479]
[43]
Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: A joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 2013; 15(6): 641-8.
[http://dx.doi.org/10.1016/j.jcyt.2013.02.006] [PMID: 23570660]
[44]
Chakraborty J, Caicci F, Roy M, Ziviani E. Investigating mitochondrial autophagy by routine transmission electron microscopy: Seeing is believing? Pharmacol Res 2020; 160: 105097.
[http://dx.doi.org/10.1016/j.phrs.2020.105097] [PMID: 32739423]
[45]
Kishi IC, Buss F. The use of Correlative Light-Electron Microscopy (CLEM) to study PINK1/Parkin-mediated mitophagy. In: Mitophagy, Hattori N, Saiki S, Eds. Methods in Molecular Biology. New York, NY: Springer 2017; 1759: p. 29-39.
[http://dx.doi.org/10.1007/7651_2017_8]
[46]
Li Z, Wu Q, Liu L, et al. Determination of Mitophagy by Electron Microscope Methods in Cell Biology. Netherlands: Elsevier 2021; Vol. 165: pp. 103-10.
[http://dx.doi.org/10.1016/bs.mcb.2020.10.015]
[47]
Peters KM, Dmochowski RR, Carr LK, et al. Autologous muscle derived cells for treatment of stress urinary incontinence in women. J Urol 2014; 192(2): 469-76.
[http://dx.doi.org/10.1016/j.juro.2014.02.047] [PMID: 24582537]
[48]
Winkler T, Perka C, Von Roth P, et al. Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty. J Cachexia Sarcopenia Muscle 2018; 9(5): 880-97.
[http://dx.doi.org/10.1002/jcsm.12316] [PMID: 30230266]
[49]
Collins CA, Olsen I, Zammit PS, et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 2005; 122(2): 289-301.
[http://dx.doi.org/10.1016/j.cell.2005.05.010] [PMID: 16051152]
[50]
Aust L, Devlin B, Foster SJ, et al. Yield of human adipose-derived adult stem cells from liposuction aspirates. Cytotherapy 2004; 6(1): 7-14.
[http://dx.doi.org/10.1080/14653240310004539] [PMID: 14985162]
[51]
Rodriguez AM, Pisani D, Dechesne CA, et al. Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med 2005; 201(9): 1397-405.
[http://dx.doi.org/10.1084/jem.20042224] [PMID: 15867092]
[52]
Vieira NM, Valadares M, Zucconi E, et al. Human adipose-derived mesenchymal stromal cells injected systemically into GRMD dogs without immunosuppression are able to reach the host muscle and express human dystrophin. Cell Transplant 2012; 21(7): 1407-17.
[http://dx.doi.org/10.3727/096368911X] [PMID: 23168016]
[53]
Rosca AM, Burlacu A. Effect of 5-azacytidine: Evidence for alteration of the multipotent ability of mesenchymal stem cells. Stem Cells Dev 2011; 20(7): 1213-21.
[http://dx.doi.org/10.1089/scd.2010.0433] [PMID: 21067364]
[54]
Zhang D, Yan K, Zhou J, et al. Myogenic differentiation of human amniotic mesenchymal cells and its tissue repair capacity on volumetric muscle loss. J Tissue Eng 2019; 10: 208223954.
[http://dx.doi.org/10.1177/2041731419887100] [PMID: 31762985]
[55]
Christman JK. 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: Mechanistic studies and their implications for cancer therapy. Oncogene 2002; 21(35): 5483-95.
[http://dx.doi.org/10.1038/sj.onc.1205699] [PMID: 12154409]
[56]
Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacol Ther 2014; 144(1): 1-11.
[http://dx.doi.org/10.1016/j.pharmthera.2014.04.006] [PMID: 24769081]
[57]
Zhang W, Huang C, Sun A, et al. Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo. Biomed Pharmacother 2018; 106: 1126-34.
[http://dx.doi.org/10.1016/j.biopha.2018.07.020] [PMID: 30119179]
[58]
Liu W, Shan LP, Dong XS, Liu XW, Ma T, Liu Z. Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury. World J Gastroenterol 2013; 19(4): 492-502.
[http://dx.doi.org/10.3748/wjg.v19.i4.492] [PMID: 23382627]
[59]
Liu S, Liu K, Sun Q, et al. Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats. J Biomed Biotechnol 2011; 2011: 305086.
[http://dx.doi.org/10.1155/2011/305086] [PMID: 21318114]
[60]
Li L, Li X, Zhang Z, et al. Effects of hydrogen-rich water on the PI3K/AKT signaling pathway in rats with myocardial ischemia-reperfusion injury. Curr Mol Med 2020; 20(5): 396-406.
[http://dx.doi.org/10.2174/1566524019666191105150709] [PMID: 31702499]
[61]
Terasaki Y, Ohsawa I, Terasaki M, et al. Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress. Am J Physiol Lung Cell Mol Physiol 2011; 301(4): L415-26.
[http://dx.doi.org/10.1152/ajplung.00008.2011] [PMID: 21764987]
[62]
Miller I, Min M, Yang C, et al. Ki67 is a graded rather than a binary marker of proliferation versus quiescence. Cell Rep 2018; 24(5): 1105-12.e5.
[http://dx.doi.org/10.1016/j.celrep.2018.06.110] [PMID: 30067968]
[63]
Wagatsuma A, Sakuma K. Mitochondria as a potential regulator of myogenesis. ScientificWorldJournal 2013; 2013: 593267.
[http://dx.doi.org/10.1155/2013/593267] [PMID: 23431256]
[64]
Tian Z, Chen Y, Yao N, et al. Role of mitophagy regulation by ROS in hepatic stellate cells during acute liver failure. Am J Physiol Gastrointest Liver Physiol 2018; 315(3): G374-84.
[http://dx.doi.org/10.1152/ajpgi.00032.2018] [PMID: 29648877]
[65]
Korolchuk VI, Miwa S, Carroll B, Von Zglinicki T. Mitochondria in cell senescence: Is mitophagy the weakest link? EBioMedicine 2017; 21: 7-13.
[http://dx.doi.org/10.1016/j.ebiom.2017.03.020] [PMID: 28330601]
[66]
Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol 2020; 21(2): 85-100.
[http://dx.doi.org/10.1038/s41580-019-0173-8] [PMID: 31636403]
[67]
Ardite E, Barbera JA, Roca J, Fernández CJC. Glutathione depletion impairs myogenic differentiation of murine skeletal muscle C2C12 cells through sustained NF-kappaB activation. Am J Pathol 2004; 165(3): 719-28.
[http://dx.doi.org/10.1016/S0002-9440(10)63335-4] [PMID: 15331397]
[68]
Chen X, Cui J, Zhai X, et al. Inhalation of hydrogen of different concentrations ameliorates spinal cord injury in mice by protecting spinal cord neurons from apoptosis, oxidative injury and mitochondrial structure damages. Cell Physiol Biochem 2018; 47(1): 176-90.
[http://dx.doi.org/10.1159/000489764] [PMID: 29763919]
[69]
Scheibye KM, Fang EF, Croteau DL, Wilson DM III, Bohr VA. Protecting the mitochondrial powerhouse. Trends Cell Biol 2015; 25(3): 158-70.
[http://dx.doi.org/10.1016/j.tcb.2014.11.002] [PMID: 25499735]
[70]
Eisner V, Picard M, Hajnóczky G. Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol 2018; 20(7): 755-65.
[http://dx.doi.org/10.1038/s41556-018-0133-0] [PMID: 29950571]
[71]
Sin J, Andres AM, Taylor DJR, et al. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy 2016; 12(2): 369-80.
[http://dx.doi.org/10.1080/15548627.2015.1115172] [PMID: 26566717]
[72]
Nichenko AS, Southern WM, Atuan M, et al. Mitochondrial maintenance via autophagy contributes to functional skeletal muscle regeneration and remodeling. Am J Physiol Cell Physiol 2016; 311(2): C190-200.
[http://dx.doi.org/10.1152/ajpcell.00066.2016] [PMID: 27281480]
[73]
Wang H, Fu J, Xu X, Yang Z, Zhang T. Rapamycin activates mitophagy and alleviates cognitive and synaptic plasticity deficits in a mouse model of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2021; 76(10): 1707-13.
[http://dx.doi.org/10.1093/gerona/glab142] [PMID: 34003967]
[74]
Wang Y, Tang C, Cai J, et al. PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury. Cell Death Dis 2018; 9(11): 1113.
[http://dx.doi.org/10.1038/s41419-018-1152-2] [PMID: 30385753]
[75]
Hu J, Zhang Y, Jiang X, et al. ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine. J Exp Clin Cancer Res 2019; 38(1): 225.
[http://dx.doi.org/10.1186/s13046-019-1201-4] [PMID: 31138329]
[76]
Shan S, Shen Z, Zhang C, Kou R, Xie K, Song F. Mitophagy protects against acetaminophen-induced acute liver injury in mice through inhibiting NLRP3 inflammasome activation. Biochem Pharmacol 2019; 169: 113643.
[http://dx.doi.org/10.1016/j.bcp.2019.113643] [PMID: 31542387]

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