Generic placeholder image

Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Perspective

Does Metformin Satisfy as an Option for Host-Directed Therapy in COVID-19?

Author(s): Pugazhenthan Thangaraju*, Atul Jindal, Sajitha Venkatesan, Meenalotchini P. Gurunthalingam, Nanditha Venkatesan and Eswaran Thangaraju

Volume 19, Issue 2, 2021

Published on: 06 October, 2020

Article ID: e270522186648 Pages: 8

DOI: 10.2174/2211352518999201006113913

Open Access Journals Promotions 2
Abstract

Metformin is a dimethyl biguanide known for its anti-hyperglycemic effects since 1922 and, thus, has been used in the treatment of Type 2 Diabetes Mellitus. Apart from this, its function as an anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-microbial agent has also been studied largely. Its effect via inhibition of respiratory complex 1 and glycerol-3-phosphate dehydrogenase (GPD2) in the mitochondria and inhibition of the mammalian target of rapamycin complex 1 (mTORC1) and activation of Adenosine Mono Phosphate dependent kinase (AMPK) in the cytoplasm are its already known mechanisms of action. With the newer proposed effects on endosome/ lysosome regulation via Na+/H+ exchangers and V-ATPase, thereby affecting autophagy, coupled with its use in ARDS owing to its immunomodulatory effects and anti-viral action, the use of metformin against the novel Coronavirus is hypothesized.

Keywords: Host, directed, therapies, metformin, COVID-19, hypothesized.

Graphical Abstract
[2]
World coronavirus statistics https://www.worldometers.info/coronavirus/
[3]
Zhang, H.; Penninger, J.M.; Li, Y.; Zhong, N.; Slutsky, A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med., 2020, 46(4), 586-590.
[http://dx.doi.org/10.1007/s00134-020-05985-9] [PMID: 32125455]
[4]
Huang, C; Wang, Y; Li, X Clinical features of patients infected with 2019 coronavirus in Wuhan, China Lancet, 2020.
[5]
Li, G; Fan, Y; Lai, Y Coronavirus infections and immune responses. J. Med. Virol., 2020.
[6]
Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol., 2017, 39(5), 529-539.
[http://dx.doi.org/10.1007/s00281-017-0629-x] [PMID: 28466096]
[7]
Zumla, A.; Hui, D.S.; Azhar, E.I.; Memish, Z.A. Reducing mortality from 2019-nCoV: host directed therapies should be an option 2019.www.lancet.com
[8]
Zumla, A.; Chan, J.F.; Azhar, E.I.; Hui, D.S.; Yuen, K.Y. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov., 2016, 15(5), 327-347.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[9]
Beigel, J.H.; Nam, H.H.; Adams, P.L.; Krafft, A.; Ince, W.L.; El-Kamary, S.S.; Sims, A.C. Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. Antiviral Res., 2019, 167, 45-67.
[http://dx.doi.org/10.1016/j.antiviral.2019.04.006] [PMID: 30974127]
[10]
Zumla, A.; Azhar, E.I.; Arabi, Y.; Alotaibi, B.; Rao, M.; McCloskey, B.; Petersen, E.; Maeurer, M. Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections. Int. J. Infect. Dis., 2015, 40, 71-74.
[http://dx.doi.org/10.1016/j.ijid.2015.09.005] [PMID: 26365771]
[11]
Zumla, A.; Maeurer, M.; Chakaya, J.; Hoelscher, M.; Ntoumi, F.; Rustomjee, R.; Vilaplana, C.; Yeboah-Manu, D.; Rasolof, V.; Munderi, P.; Singh, N.; Aklillu, E.; Padayatchi, N.; Macete, E.; Kapata, N.; Mulenga, M.; Kibiki, G.; Mfinanga, S.; Nyirenda, T.; Maboko, L.; Garcia-Basteiro, A.; Rakotosamimanana, N.; Bates, M.; Mwaba, P.; Reither, K.; Gagneux, S.; Edwards, S.; Mfinanga, E.; Abdulla, S.; Cardona, P.J.; Russell, J.B.; Gant, V.; Noursadeghi, M.; Elkington, P.; Bonnet, M.; Menendez, C.; Dieye, T.N.; Diarra, B.; Maiga, A.; Aseffa, A.; Parida, S.; Wejse, C.; Petersen, E.; Kaleebu, P.; Oliver, M.; Craig, G.; Corrah, T.; Tientcheu, L.; Antonio, M.; Rao, M.; McHugh, T.D.; Sheikh, A.; Ippolito, G.; Ramjee, G.; Kaufmann, S.H.; Churchyard, G.; Steyn, A.; Grobusch, M.; Sanne, I.; Martinson, N.; Madansein, R.; Wilkinson, R.J.; Mayosi, B.; Schito, M.; Wallis, R.S. Host-Directed Therapies Network. Towards host-directed therapies for tuberculosis. Nat. Rev. Drug Discov., 2015, 14(8), 511-512.
[http://dx.doi.org/10.1038/nrd4696] [PMID: 26184493]
[12]
Zumla, A.; Maeurer, M. Host-DirectedTherapiesNetwork(HDT-NET)Consortium. Host-Directed Therapies Network HDT-NET Consortium. Host-Directed Therapies for tackling Multi-Drug Resistant TB - learning from the Pasteur-Bechamp debates. Clin. Infect. Dis., 2015, civ631
[13]
Tan, E.L.; Ooi, E.E.; Lin, C.Y.; Tan, H.C.; Ling, A.E.; Lim, B.; Stanton, L.W. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg. Infect. Dis., 2004, 10(4), 581-586.
[http://dx.doi.org/10.3201/eid1004.030458] [PMID: 15200845]
[14]
Savarino, A.; Boelaert, J.R.; Cassone, A.; Majori, G.; Cauda, R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect. Dis., 2003, 3(11), 722-727.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[15]
Gautret, P.; Lagier, J.C.; Parola, P.; Hoang, V.T.; Meddeb, L.; Mailhe, M.; Doudier, B.; Courjon, J.; Giordanengo, V.; Vieira, V.E.; Tissot Dupont, H.; Honoré, S.; Colson, P.; Chabrière, E.; La Scola, B.; Rolain, J.M.; Brouqui, P.; Raoult, D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents, 2020, 56(1)105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[16]
Rena, G.; Hardie, D.G.; Pearson, E.R. The mechanisms of action of metformin. Diabetologia, 2017, 60(9), 1577-1585.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[17]
An, H.; He, L. Current understanding of metformin effect on the control of hyperglycemia in diabetes. J. Endocrinol., 2016, 228(3), R97-R106.
[http://dx.doi.org/10.1530/JOE-15-0447] [PMID: 26743209]
[18]
Cameron, A.R.; Morrison, V.L.; Levin, D.; Mohan, M.; Forteath, C.; Beall, C.; McNeilly, A.D.; Balfour, D.J.; Savinko, T.; Wong, A.K.; Viollet, B.; Sakamoto, K.; Fagerholm, S.C.; Foretz, M.; Lang, C.C.; Rena, G. Anti‐inflammatory effects of metformin irrespective of diabetes status. Circ. Res., 2016, 119(5), 652-665.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308445] [PMID: 27418629]
[19]
Liu, G.; Wu, K.; Zhang, L.; Dai, J.; Huang, W.; Lin, L.; Ge, P.; Luo, F.; Lei, H. Metformin attenuated endotoxin-induced acute myocarditis via activating AMPK. Int. Immunopharmacol., 2017, 47, 166-172.
[http://dx.doi.org/10.1016/j.intimp.2017.04.002] [PMID: 28410530]
[20]
Chen, C.Z.; Hsu, C.H.; Li, C.Y.; Hsiue, T.R. Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort. J. Asthma, 2017, 54(10), 1019-1025.
[http://dx.doi.org/10.1080/02770903.2017.1283698] [PMID: 28135899]
[21]
Grant, PJ Beneficial effects of metformin on haemostasis and vascular function in man Diabetes Metab, 2003, 29(4), 6S44-52.
[http://dx.doi.org/10.1016/S1262-3636(03)72787-6]
[22]
Pernicova, I.; Korbonits, M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol., 2014, 10(3), 143-156.
[http://dx.doi.org/10.1038/nrendo.2013.256] [PMID: 24393785]
[23]
Wu, H.; Esteve, E.; Tremaroli, V.; Khan, M.T.; Caesar, R.; Mannerås-Holm, L.; Ståhlman, M.; Olsson, L.M.; Serino, M.; Planas-Fèlix, M.; Xifra, G.; Mercader, J.M.; Torrents, D.; Burcelin, R.; Ricart, W.; Perkins, R.; Fernàndez-Real, J.M.; Bäckhed, F. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med., 2017, 23(7), 850-858.
[http://dx.doi.org/10.1038/nm.4345] [PMID: 28530702]
[24]
Ansari, G.; Mojtahedzadeh, M.; Kajbaf, F.; Najafi, A.; Khajavi, M.R.; Khalili, H.; Rouini, M.R.; Ahmadi, H.; Abdollahi, M. How does blood glucose control with metformin influence intensive insulin protocols? Evidence for involvement of oxidative stress and inflammatory cytokines. Adv. Ther., 2008, 25(7), 681-702.
[http://dx.doi.org/10.1007/s12325-008-0075-1] [PMID: 18636232]
[25]
Madiraju, A.K.; Erion, D.M.; Rahimi, Y.; Zhang, X.M.; Braddock, D.T.; Albright, R.A.; Prigaro, B.J.; Wood, J.L.; Bhanot, S.; MacDonald, M.J.; Jurczak, M.J.; Camporez, J.P.; Lee, H.Y.; Cline, G.W.; Samuel, V.T.; Kibbey, R.G.; Shulman, G.I. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature, 2014, 510(7506), 542-546.
[http://dx.doi.org/10.1038/nature13270] [PMID: 24847880]
[26]
Kim, J.; Kundu, M.; Viollet, B.; Guan, K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol., 2011, 13(2), 132-141.
[http://dx.doi.org/10.1038/ncb2152] [PMID: 21258367]
[27]
Mihaylova, M.M.; Shaw, R.J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol., 2011, 13(9), 1016-1023.
[http://dx.doi.org/10.1038/ncb2329] [PMID: 21892142]
[28]
Tsaknis, G.; Siempos, I.I.; Kopterides, P.; Maniatis, N.A.; Magkou, C.; Kardara, M.; Panoutsou, S.; Kotanidou, A.; Roussos, C.; Armaganidis, A. Metformin attenuates ventilator-induced lung injury. Crit. Care, 2012, 16(4), R134.
[http://dx.doi.org/10.1186/cc11439] [PMID: 22827994]
[29]
He, L.; Wondisford, F.E. Metformin action: concentrations matter. Cell Metab., 2015, 21(2), 159-162.
[http://dx.doi.org/10.1016/j.cmet.2015.01.003] [PMID: 25651170]
[30]
Owen, MR; Doran, E; Halestrap, AP Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain Biochem J., 2000, Pt 3, 607-614.
[31]
Hardie, D.G.; Ross, F.A.; Hawley, S.A. AMP-activated protein kinase: a target for drugs both ancient and modern. Chem. Biol., 2012, 19(10), 1222-1236.
[http://dx.doi.org/10.1016/j.chembiol.2012.08.019] [PMID: 23102217]
[32]
Kim, J.; You, Y.J. Regulation of organelle function by metformin. IUBMB Life, 2017, 69(7), 459-469.
[http://dx.doi.org/10.1002/iub.1633] [PMID: 28444922]
[33]
Zhang, C.S.; Li, M.; Ma, T.; Zong, Y.; Cui, J.; Feng, J.W.; Wu, Y.Q.; Lin, S.Y.; Lin, S.C. Metformin activates AMPK through the lysosomal pathway. Cell Metab., 2016, 24(4), 521-522.
[http://dx.doi.org/10.1016/j.cmet.2016.09.003] [PMID: 27732831]
[34]
Xu, J.; Xu, L.; Lau, Y.S.; Gao, Y.; Moore, S.A.; Han, R. A novel ANO5 splicing variant in a LGMD2L patient leads to production of a truncated aggregation-prone Ano5 peptide. J. Pathol. Clin. Res., 2018, 4(2), 135-145.
[http://dx.doi.org/10.1002/cjp2.92] [PMID: 29665321]
[35]
Zhang, Y.L.; Guo, H.; Zhang, C.S.; Lin, S.Y.; Yin, Z.; Peng, Y.; Luo, H.; Shi, Y.; Lian, G.; Zhang, C.; Li, M.; Ye, Z.; Ye, J.; Han, J.; Li, P.; Wu, J.W.; Lin, S.C. AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. Cell Metab., 2013, 18(4), 546-555.
[http://dx.doi.org/10.1016/j.cmet.2013.09.005] [PMID: 24093678]
[36]
Sharifi, A.H.; Mohammadi, M.; Fakharzadeh, E.; Zamini, H.; Zaer-Rezaee, H.; Jabbari, H.; Merat, S. Efficacy of adding metformin to pegylated interferon and ribavirin in treatment naïve patients with chronic hepatitis C: a randomized double-blind controlled trial. Middle East J. Dig. Dis., 2014, 6(1), 13-17.
[PMID: 24829699]
[37]
Nkontchou, G.; Cosson, E.; Aout, M.; Mahmoudi, A.; Bourcier, V.; Charif, I.; Ganne-Carrie, N.; Grando-Lemaire, V.; Vicaut, E.; Trinchet, J.C.; Beaugrand, M. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J. Clin. Endocrinol. Metab., 2011, 96(8), 2601-2608.
[http://dx.doi.org/10.1210/jc.2010-2415] [PMID: 21752887]
[38]
deLemos, A.S.; Chung, R.T. Hepatitis C treatment: an incipient therapeutic revolution. Trends Mol. Med., 2014, 20(6), 315-321.
[http://dx.doi.org/10.1016/j.molmed.2014.02.002] [PMID: 24636306]
[39]
Fitch, K.; Abbara, S.; Lee, H.; Stavrou, E.; Sacks, R.; Michel, T.; Hemphill, L.; Torriani, M.; Grinspoon, S. Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome. AIDS, 2012, 26(5), 587-597.
[http://dx.doi.org/10.1097/QAD.0b013e32834f33cc] [PMID: 22112605]
[40]
Harrison, S.A.; Hamzeh, F.M.; Han, J.; Pandya, P.K.; Sheikh, M.Y.; Vierling, J.M. Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin. Hepatology, 2012, 56(2), 464-473.
[http://dx.doi.org/10.1002/hep.25661] [PMID: 22334369]
[41]
Prantner, D.; Perkins, D.J.; Vogel, S.N. AMP-activated kinase (AMPK) promotes innate immunity and antiviral defense through modulation of stimulator of interferon genes (STING) signaling. J. Biol. Chem., 2017, 292(1), 292-304.
[http://dx.doi.org/10.1074/jbc.M116.763268] [PMID: 27879319]
[42]
Zhao, H.; Lin, W.; Kumthip, K.; Cheng, D.; Fusco, D.N.; Hofmann, O.; Jilg, N.; Tai, A.W.; Goto, K.; Zhang, L.; Hide, W.; Jang, J.Y.; Peng, L.F.; Chung, R.T. A functional genomic screen reveals novel host genes that mediate interferon-alpha’s effects against hepatitis C virus. J. Hepatol., 2012, 56(2), 326-333.
[http://dx.doi.org/10.1016/j.jhep.2011.07.026] [PMID: 21888876]
[43]
Der, S.D.; Zhou, A.; Williams, B.R.; Silverman, R.H. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. USA, 1998, 95(26), 15623-15628.
[http://dx.doi.org/10.1073/pnas.95.26.15623] [PMID: 9861020]
[44]
Horner, S.M.; Gale, M., Jr Regulation of hepatic innate immunity by hepatitis C virus. Nat. Med., 2013, 19(7), 879-888.
[http://dx.doi.org/10.1038/nm.3253] [PMID: 23836238]
[45]
Darnell, J.E., Jr; Kerr, I.M.; Stark, G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science, 1994, 264(5164), 1415-1421.
[http://dx.doi.org/10.1126/science.8197455] [PMID: 8197455]
[46]
Goto, K.; Lin, W.; Zhang, L.; Jilg, N.; Shao, R.X.; Schaefer, E.A.; Zhao, H.; Fusco, D.N.; Peng, L.F.; Kato, N.; Chung, R.T. The AMPK-related kinase SNARK regulates hepatitis C virus replication and pathogenesis through enhancement of TGF-β signaling. J. Hepatol., 2013, 59(5), 942-948.
[http://dx.doi.org/10.1016/j.jhep.2013.06.025] [PMID: 23831117]
[47]
Huang, H.; Kang, R.; Wang, J.; Luo, G.; Yang, W.; Zhao, Z. Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to induce autophagy. Autophagy, 2013, 9(2), 175-195.
[http://dx.doi.org/10.4161/auto.22791] [PMID: 23169238]
[48]
del Campo, J.A.; García-Valdecasas, M.; Rojas, L.; Rojas, Á.; Romero-Gómez, M. The hepatitis C virus modulates insulin signaling pathway in vitro promoting insulin resistance. PLoS One, 2012, 7(10)e47904
[http://dx.doi.org/10.1371/journal.pone.0047904] [PMID: 23133528]
[49]
Forno, E. Asthma and diabetes: Does treatment with metformin improve asthma? Respirology, 2016, 21(7), 1144-1145.
[http://dx.doi.org/10.1111/resp.12869] [PMID: 27533627]
[50]
Park cs, BanG Br, kWon hs, Moon ka, kiM tB, lee ky, Moon hB, cho ys. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem. Pharmacol., 2012, 84, 1660-1670.
[http://dx.doi.org/10.1016/j.bcp.2012.09.025]
[51]
Liu, Y.; Yang, F.; Ma, W.; Sun, Q. Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytes in vitro via mTOR-signaling pathway. Pharm. Biol., 2015, , 1-6.
[PMID: 26305116]
[52]
Kim, J.; Kwak, H.J.; Cha, J.Y.; Jeong, Y.S.; Rhee, S.D.; Kim, K.R.; Cheon, H.G. Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction. J. Biol. Chem., 2014, 289(33), 23246-23255.
[http://dx.doi.org/10.1074/jbc.M114.577908] [PMID: 24973221]
[53]
Arai, M.; Uchiba, M.; Komura, H.; Mizuochi, Y.; Harada, N.; Okajima, K. Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro. J. Pharmacol. Exp. Ther., 2010, 334(1), 206-213.
[http://dx.doi.org/10.1124/jpet.109.164970] [PMID: 20371705]
[54]
Hattori, Y.; Suzuki, K.; Hattori, S.; Kasai, K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 2006, 47(6), 1183-1188.
[http://dx.doi.org/10.1161/01.HYP.0000221429.94591.72] [PMID: 16636195]
[55]
Hyun, B.; Shin, S.; Lee, A.; Lee, S.; Song, Y.; Ha, N.J.; Cho, K.H.; Kim, K. Metformin Down-regulates TNF-α Secretion via Suppression of Scavenger Receptors in Macrophages. Immune Netw., 2013, 13(4), 123-132.
[http://dx.doi.org/10.4110/in.2013.13.4.123] [PMID: 24009539]
[56]
Fan, E.; Brodie, D.; Slutsky, A.S. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA, 2018, 319(7), 698-710.
[http://dx.doi.org/10.1001/jama.2017.21907] [PMID: 29466596]
[57]
Bellani, G.; Laffey, J.G.; Pham, T.; Fan, E.; Brochard, L.; Esteban, A.; Gattinoni, L.; van Haren, F.; Larsson, A.; McAuley, D.F.; Ranieri, M.; Rubenfeld, G.; Thompson, B.T.; Wrigge, H.; Slutsky, A.S.; Pesenti, A. LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA, 2016, 315(8), 788-800.
[http://dx.doi.org/10.1001/jama.2016.0291] [PMID: 26903337]
[58]
Han, S.; Mallampalli, R.K. The acute respiratory distress syndrome: from mechanism to translation. J. Immunol., 2015, 194(3), 855-860.
[http://dx.doi.org/10.4049/jimmunol.1402513] [PMID: 25596299]
[59]
Matthay, M.A.; Zemans, R.L. The acute respiratory distress syndrome: pathogenesis and treatment. Annu. Rev. Pathol., 2011, 6, 147-163.
[http://dx.doi.org/10.1146/annurev-pathol-011110-130158] [PMID: 20936936]
[60]
Thompson, B.T.; Chambers, R.C.; Liu, K.D. Acute respiratory distress syndrome. N. Engl. J. Med., 2017, 377(6), 562-572.
[http://dx.doi.org/10.1056/NEJMra1608077] [PMID: 28792873]
[61]
Cheng, O.Z.; Palaniyar, N. NET balancing: a problem in inflammatory lung diseases. Front. Immunol., 2013, 4, 1.
[http://dx.doi.org/10.3389/fimmu.2013.00001] [PMID: 23355837]
[62]
Saffarzadeh, M.; Juenemann, C.; Queisser, M.A.; Lochnit, G.; Barreto, G.; Galuska, S.P.; Lohmeyer, J.; Preissner, K.T. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One, 2012, 7(2): e32366
[http://dx.doi.org/10.1371/journal.pone.0032366] [PMID: 22389696]
[63]
Lefrançais, E.; Mallavia, B.; Zhuo, H.; Calfee, C.S.; Looney, M.R. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight, 2018, 3(3): e98178
[http://dx.doi.org/10.1172/jci.insight.98178] [PMID: 29415887]
[64]
Tsoyi, K.; Jang, H.J.; Nizamutdinova, I.T.; Kim, Y.M.; Lee, Y.S.; Kim, H.J.; Seo, H.G.; Lee, J.H.; Chang, K.C. Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice. Br. J. Pharmacol., 2011, 162(7), 1498-1508.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01126.x] [PMID: 21091653]
[65]
Zmijewski, J.W.; Bae, H.B.; Deshane, J.S.; Peterson, C.B.; Chaplin, D.D.; Abraham, E. Inhibition of neutrophil apoptosis by PAI-1. Am. J. Physiol. Lung Cell. Mol. Physiol., 2011, 301(2), L247-L254.
[http://dx.doi.org/10.1152/ajplung.00075.2011] [PMID: 21622848]
[66]
Grégoire, M.; Uhel, F.; Lesouhaitier, M.; Gacouin, A.; Guirriec, M.; Mourcin, F.; Dumontet, E.; Chalin, A.; Samson, M.; Berthelot, L.L.; Tissot, A.; Kerjouan, M.; Jouneau, S.; Le Tulzo, Y.; Tarte, K.; Zmijewski, J.W.; Tadié, J.M. Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS. Eur. Respir. J., 2018, 52(2)1702590
[http://dx.doi.org/10.1183/13993003.02590-2017] [PMID: 29946009]
[67]
Hardie, D.G. AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr. Opin. Cell Biol., 2015, 33, 1-7.
[http://dx.doi.org/10.1016/j.ceb.2014.09.004] [PMID: 25259783]
[68]
Li, M.; Li, X.; Zhang, H.; Lu, Y. Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment. Front. Physiol., 2018, 9, 1039.
[http://dx.doi.org/10.3389/fphys.2018.01039] [PMID: 30108523]
[69]
Zarember, K.A.; Godowski, P.J. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J. Immunol., 2002, 168(2), 554-561. [published correction appears in J Immunol 2002 Jul 15;169(2):1136].
[http://dx.doi.org/10.4049/jimmunol.168.2.554] [PMID: 11777946]
[70]
Huugen, D.; Xiao, H.; van Esch, A.; Falk, R.J.; Peutz-Kootstra, C.J.; Buurman, W.A.; Tervaert, J.W.; Jennette, J.C.; Heeringa, P. Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-alpha. Am. J. Pathol., 2005, 167(1), 47-58.
[http://dx.doi.org/10.1016/S0002-9440(10)62952-5] [PMID: 15972951]
[71]
Lucas, R.; Verin, A.D.; Black, S.M.; Catravas, J.D. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem. Pharmacol., 2009, 77(12), 1763-1772.
[http://dx.doi.org/10.1016/j.bcp.2009.01.014] [PMID: 19428331]
[72]
Yu, L.L.; Zhu, M.; Huang, Y.; Zhao, Y.M.; Wen, J.J.; Yang, X.J.; Wu, P. Metformin relieves acute respiratory distress syndrome by reducing miR-138 expression. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(16), 5355-5363.
[PMID: 30178862]

© 2024 Bentham Science Publishers | Privacy Policy