Review – Nutraceuticals Can Target Asthmatic Bronchoconstriction: NADPH Oxidase-Dependent Oxidative Stress, RhoA and Calcium Dynamics

References

• Fanta CH. Asthma. N Engl J Med. 2009;360(10):1002–1014. doi:10.1056/NEJMra0804579
   PubMed Web of Science ®Google Scholar
• Bédard A, Li Z, Ait-Hadad W, et al. The role of nutritional factors in asthma: challenges and opportunities for epidemiological research. Int J Environ Res Public Health. 2021;18(6):3013. doi:10.3390/ijerph18063013
   PubMed Web of Science ®Google Scholar
• Wang M, Yao Y, Jiang S, Tao F, Tang R, Sun J. How to control asthma with personalized management: where do we stand now? Curr Drug Metab. 2018;19(14):1188–1198. doi:10.2174/1389200219666180129111810
   Web of Science ®Google Scholar
• Sozańska B, Sikorska-Szaflik H. Diet modifications in primary prevention of asthma. where do we stand? Nutrients. 2021;13(1):173. doi:10.3390/nu13010173
   Web of Science ®Google Scholar
• KleinJan A. Airway inflammation in asthma: key players beyond the Th2 pathway. Curr Opin Pulm Med. 2016;22(1):46–52. doi:10.1097/MCP.0000000000000224
   PubMed Web of Science ®Google Scholar
• Yap HM, Israf DA, Harith HH, Tham CL, Sulaiman MR. Crosstalk between signaling pathways involved in the regulation of airway smooth muscle cell hyperplasia. Front Pharmacol. 2019;10:1148. doi:10.3389/fphar.2019.01148
   PubMed Web of Science ®Google Scholar
• Zhang Y, Saradna A, Ratan R, et al. RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets. Clin Transl Immunol. 2020;9(5):e01134. doi:10.1002/cti2.1134
   PubMed Web of Science ®Google Scholar
• Siehler S. Regulation of RhoGEF proteins by G12/13-coupled receptors. Br J Pharmacol. 2009;158(1):41–49. doi:10.1111/j.1476-5381.2009.00121.x
   PubMed Web of Science ®Google Scholar
• Walsh MP, Susnjar M, Deng J, Sutherland C, Kiss E, Wilson DP. Phosphorylation of the protein phosphatase type 1 inhibitor protein CPI-17 by protein kinase C. Methods Mol Biol. 2007;365:209–223. doi:10.1385/1-59745-267-X:209
   Google Scholar
• Brueggemann LI, Kakad PP, Love RB, et al. Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy. Am J Physiol Lung Cell Mol Physiol. 2012;302(1):L120–L132. doi:10.1152/ajplung.00194.2011
   PubMed Web of Science ®Google Scholar
• Haick JM, Brueggemann LI, Cribbs LL, Denning MF, Schwartz J, Byron KL. PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L822–L834. doi:10.1152/ajplung.00567.2016
   PubMed Web of Science ®Google Scholar
• Ikebe M, Hartshorne DJ. Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase. J Biol Chem. 1985;260(18):10027–10031. doi:10.1016/S0021-9258(17)39206-2
   Web of Science ®Google Scholar
• Taylor KA, Feig M, Brooks CL III, Fagnant PM, Lowey S, Trybus KM. Role of the essential light chain in the activation of smooth muscle myosin by regulatory light chain phosphorylation. J Struct Biol. 2014;185(3):375–382. doi:10.1016/j.jsb.2013.12.008
   Web of Science ®Google Scholar
• Sutcliffe A, Hollins F, Gomez E, et al. Increased nicotinamide adenine dinucleotide phosphate oxidase 4 expression mediates intrinsic airway smooth muscle hypercontractility in asthma. Am J Respir Crit Care Med. 2012;185(3):267–274. doi:10.1164/rccm.201107-1281OC
   PubMed Web of Science ®Google Scholar
• Lu W, Kang J, Hu K, et al. The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia. Sleep Breath. 2017;21(3):667–677. doi:10.1007/s11325-016-1449-2
   PubMed Web of Science ®Google Scholar
• Jin L, Ying Z, Webb RC. Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. Am J Physiol Heart Circ Physiol. 2004;287(4):H1495–H1500. doi:10.1152/ajpheart.01006.2003
   PubMed Web of Science ®Google Scholar
• Jernigan NL, Walker BR, Resta TC. Reactive oxygen species mediate RhoA/Rho kinase-induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia. Am J Physiol Lung Cell Mol Physiol. 2008;295(3):L515–L529. doi:10.1152/ajplung.00355.2007
   PubMed Web of Science ®Google Scholar
• Mahavadi S, Sriwai W, Manion O, Grider JR, Murthy KS. Diabetes-induced oxidative stress mediates upregulation of RhoA/Rho kinase pathway and hypercontractility of gastric smooth muscle. PLoS One. 2017;12(7):e0178574. doi:10.1371/journal.pone.0178574
   Web of Science ®Google Scholar
• Sakai H, Suto W, Kai Y, Chiba Y. Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma. J Smooth Muscle Res. 2017;53:37–47. doi:10.1540/jsmr.53.37
   PubMedGoogle Scholar
• Morelli A, Filippi S, Sandner P, et al. Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/Rho kinase signaling pathway in spontaneously hypertensive rats. J Sex Med. 2009;6(6):1594–1608. doi:10.1111/j.1743-6109.2009.01249.x
   Web of Science ®Google Scholar
• Aburima A, Walladbegi K, Wake JD, Naseem KM. cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway. J Thromb Haemost. 2017;15(8):1668–1678. doi:10.1111/jth.13738
   Web of Science ®Google Scholar
• Nalli AD, Rajagopal S, Mahavadi S, Grider JR, Murthy KS. Inhibition of RhoA-dependent pathway and contraction by endogenous hydrogen sulfide in rabbit gastric smooth muscle cells. Am J Physiol Cell Physiol. 2015;308(6):C485–C495. doi:10.1152/ajpcell.00280.2014
   Web of Science ®Google Scholar
• Nalli AD, Wang H, Bhattacharya S, Blakeney BA, Murthy KS. Inhibition of RhoA/Rho kinase pathway and smooth muscle contraction by hydrogen sulfide. Pharmacol Res Perspect. 2017;5(5):e00343. doi:10.1002/prp2.343
   Web of Science ®Google Scholar
• Zhou Z, Martin E, Sharina I, et al. Regulation of soluble guanylyl cyclase redox state by hydrogen sulfide. Pharmacol Res. 2016;111:556–562. doi:10.1016/j.phrs.2016.06.029
   PubMed Web of Science ®Google Scholar
• Coletta C, Papapetropoulos A, Erdelyi K, et al. Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A. 2012;109(23):9161–9166. doi:10.1073/pnas.1202916109
   PubMed Web of Science ®Google Scholar
• Sun Y, Huang Y, Yu W, et al. Sulfhydration-associated phosphodiesterase 5A dimerization mediates vasorelaxant effect of hydrogen sulfide. Oncotarget. 2017;8(19):31888–31900. doi:10.18632/oncotarget.16649
   PubMedGoogle Scholar
• Brar SS, Kennedy TP, Whorton AR, Murphy TM, Chitano P, Hoidal JR. Requirement for reactive oxygen species in serum-induced and platelet-derived growth factor-induced growth of airway smooth muscle. J Biol Chem. 1999;274(28):20017–20026. doi:10.1074/jbc.274.28.20017
   Web of Science ®Google Scholar
• Brar SS, Kennedy TP, Sturrock AB, et al. NADPH oxidase promotes NF-kappaB activation and proliferation in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2002;282(4):L782–L795. doi:10.1152/ajplung.00206.2001
   Web of Science ®Google Scholar
• Sturrock A, Huecksteadt TP, Norman K, et al. Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007;292(6):L1543–L1555. doi:10.1152/ajplung.00430.2006
   Web of Science ®Google Scholar
• Thomas B, Rutman A, Hirst RA, et al. Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. J Allergy Clin Immunol. 2010;126(4):722–729. doi:10.1016/j.jaci.2010.05.046
   PubMed Web of Science ®Google Scholar
• Wan WY, Hollins F, Haste L, et al. NADPH Oxidase-4 overexpression is associated with epithelial ciliary dysfunction in neutrophilic asthma. Chest. 2016;149(6):1445–1459. doi:10.1016/j.chest.2016.01.024
   Web of Science ®Google Scholar
• Uhm TG, Kim BS, Chung IY. Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma. Allergy Asthma Immunol Res. 2012;4(2):68–79. doi:10.4168/aair.2012.4.2.68
   PubMed Web of Science ®Google Scholar
• Chin JE, Hatfield CA, Winterrowd GE, et al. Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1. Am J Physiol. 1997;272(2 Pt 1):L219–L229. doi:10.1152/ajplung.1997.272.2.L219
   Web of Science ®Google Scholar
• Sagara H, Matsuda H, Wada N, et al. A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma. Int Arch Allergy Immunol. 1997;112(3):287–294. doi:10.1159/000237468
   Web of Science ®Google Scholar
• Matheny HE, Deem TL, Cook-Mills JM. Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase. J Immunol. 2000;164(12):6550–6559. doi:10.4049/jimmunol.164.12.6550
   PubMed Web of Science ®Google Scholar
• Deem TL, Cook-Mills JM. Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. Blood. 2004;104(8):2385–2393. doi:10.1182/blood-2004-02-0665
   PubMed Web of Science ®Google Scholar
• Abdala-Valencia H, Earwood J, Bansal S, et al. Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma. Am J Physiol Lung Cell Mol Physiol. 2007;292(5):L1111–L1125. doi:10.1152/ajplung.00208.2006
   Web of Science ®Google Scholar
• Suzuki Y, Yoshimaru T, Inoue T, Niide O, Ra C. Role of oxidants in mast cell activation. Chem Immunol Allergy. 2005;87:32–42.
   PubMedGoogle Scholar
• Inoue T, Suzuki Y, Yoshimaru T, Ra C. Reactive oxygen species produced up- or downstream of calcium influx regulate proinflammatory mediator release from mast cells: role of NADPH oxidase and mitochondria. Biochim Biophys Acta. 2008;1783(5):789–802. doi:10.1016/j.bbamcr.2007.12.004
   Web of Science ®Google Scholar
• Cho KJ, Seo JM, Lee MG, Kim JH. BLT2 Is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines. J Immunol. 2010;185(10):6329–6337. doi:10.4049/jimmunol.1001213
   Web of Science ®Google Scholar
• Kim SY, Moon KA, Jo HY, et al. Anti-inflammatory effects of apocynin, an inhibitor of NADPH oxidase, in airway inflammation. Immunol Cell Biol. 2012;90(4):441–448. doi:10.1038/icb.2011.60
   PubMed Web of Science ®Google Scholar
• Peters EA, Hiltermann JT, Stolk J. Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med. 2001;31(11):1442–1447. doi:10.1016/S0891-5849(01)00725-0
   PubMed Web of Science ®Google Scholar
• Lanone S, Bloc S, Foresti R, et al. Bilirubin decreases nos2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats. FASEB J. 2005;19(13):1890–1892. doi:10.1096/fj.04-2368fje
   PubMed Web of Science ®Google Scholar
• Matsumoto H, Ishikawa K, Itabe H, Maruyama Y. Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction. Mol Cell Biochem. 2006;291(1–2):21–28. doi:10.1007/s11010-006-9190-y
   PubMed Web of Science ®Google Scholar
• Jiang F, Roberts SJ, Datla S, Dusting GJ. NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial cells. Hypertension. 2006;48(5):950–957. doi:10.1161/01.HYP.0000242336.58387.1f
   PubMed Web of Science ®Google Scholar
• Datla SR, Dusting GJ, Mori TA, Taylor CJ, Croft KD, Jiang F. Induction of heme oxygenase-1 in vivo suppresses NADPH oxidase derived oxidative stress. Hypertension. 2007;50(4):636–642. doi:10.1161/HYPERTENSIONAHA.107.092296
   PubMed Web of Science ®Google Scholar
• Ohrui T, Yasuda H, Yamaya M, Matsui T, Sasaki H. Transient relief of asthma symptoms during jaundice: a possible beneficial role of bilirubin. Tohoku J Exp Med. 2003;199(3):193–196. doi:10.1620/tjem.199.193
   Web of Science ®Google Scholar
• Kim DE, Lee Y, Kim M, Lee S, Jon S, Lee SH. Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma. Biomaterials. 2017;140:37–44. doi:10.1016/j.biomaterials.2017.06.014
   PubMed Web of Science ®Google Scholar
• Keshavan P, Deem TL, Schwemberger SJ, Babcock GF, Cook-Mills JM, Zucker SD. Unconjugated bilirubin inhibits VCAM-1-mediated transendothelial leukocyte migration. J Immunol. 2005;174(6):3709–3718. doi:10.4049/jimmunol.174.6.3709
   PubMed Web of Science ®Google Scholar
• Samb A, Taille C, Almolki A, et al. Heme oxygenase modulates oxidant-signaled airway smooth muscle contractility: role of bilirubin. Am J Physiol Lung Cell Mol Physiol. 2002;283(3):L596–L603. doi:10.1152/ajplung.00446.2001
   PubMed Web of Science ®Google Scholar
• Taille C, Almolki A, Benhamed M, et al. Heme oxygenase inhibits human airway smooth muscle proliferation via a bilirubin-dependent modulation of ERK1/2 phosphorylation. J Biol Chem. 2003;278(29):27160–27168. doi:10.1074/jbc.M300364200
   Web of Science ®Google Scholar
• Takamiya R, Murakami M, Kajimura M, et al. Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role. Am J Physiol Heart Circ Physiol. 2002;283(3):H861–H870. doi:10.1152/ajpheart.00740.2001
   Web of Science ®Google Scholar
• Matsushima M, Takagi K, Ogawa M, et al. Heme oxygenase-1 mediates the anti-allergic actions of quercetin in rodent mast cells. Inflamm Res. 2009;58(10):705–715. doi:10.1007/s00011-009-0039-1
   PubMed Web of Science ®Google Scholar
• McCarty MF. Clinical potential of Spirulina as a source of phycocyanobilin. J Med Food. 2007;10(4):566–570. doi:10.1089/jmf.2007.621
   PubMed Web of Science ®Google Scholar
• Terry MJ, Maines MD, Lagarias JC. Inactivation of phytochrome- and phycobiliprotein-chromophore precursors by rat liver biliverdin reductase. J Biol Chem. 1993;268(35):26099–26106. doi:10.1016/S0021-9258(19)74286-0
   Web of Science ®Google Scholar
• Zheng J, Inoguchi T, Sasaki S, et al. Phycocyanin and phycocyanobilin from spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress. Am J Physiol Regul Integr Comp Physiol. 2013;304:R110–R120. doi:10.1152/ajpregu.00648.2011
   PubMed Web of Science ®Google Scholar
• Romay C, Gonzalez R, Ledon N, Remirez D, Rimbau V. C-phycocyanin: a biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr Protein Pept Sci. 2003;4(3):207–216. doi:10.2174/1389203033487216
   PubMed Web of Science ®Google Scholar
• Riss J, Décordé K, Sutra T, et al. Phycobiliprotein C-phycocyanin from spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric Food Chem. 2007;55(19):7962–7967. doi:10.1021/jf070529g
   PubMed Web of Science ®Google Scholar
• Labhe RU, Mani UV, Iyer UM, Mishra M, Jani K, Bhattacharya A. The effect of spirulina in the treatment of bronchial asthma. J Nutraceuticals Func Med Foods. 2015;3(4):53–60. doi:10.1300/J133v03n04_06
   Google Scholar
• Horsfall LJ, Rait G, Walters K, et al. Serum bilirubin and risk of respiratory disease and death. JAMA. 2011;305(7):691–697. doi:10.1001/jama.2011.124
   PubMed Web of Science ®Google Scholar
• Wang HD, Yamaya M, Okinaga S, et al. Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. Am J Respir Crit Care Med. 2002;165(3):406–411. doi:10.1164/ajrccm.165.3.2003149
   PubMed Web of Science ®Google Scholar
• Ohrui T, Higuchi M, Kanda A, Matsui T, Sato E, Sasaki H. A patient with exacerbation of idiopathic pulmonary fibrosis which was resolved probably due to the coexisting hyperbilirubinemia? Tohoku J Exp Med. 2001;193(3):245–249. doi:10.1620/tjem.193.245
   Web of Science ®Google Scholar
• Waypa GB, Guzy R, Mungai PT, et al. Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells. Circ Res. 2006;99(9):970–978. doi:10.1161/01.RES.0000247068.75808.3f
   PubMed Web of Science ®Google Scholar
• Rathore R, Zheng YM, Niu CF, et al. Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the mitochondrial ROS-PKCepsilon signaling axis in pulmonary artery smooth muscle cells. Free Radic Biol Med. 2008;45(9):1223–1231. doi:10.1016/j.freeradbiomed.2008.06.012
   Web of Science ®Google Scholar
• Wang YX, Zheng YM. ROS-dependent signaling mechanisms for hypoxic Ca(2+) responses in pulmonary artery myocytes. Antioxid Redox Signal. 2010;12(5):611–623. doi:10.1089/ars.2009.2877
   Web of Science ®Google Scholar
• McCarty MF, Barroso-Aranda J, Contreras F. Practical strategies for targeting NF-kappaB and NADPH oxidase may improve survival during lethal influenza epidemics. Med Hypotheses. 2010;74(1):18–20. doi:10.1016/j.mehy.2009.04.052
   PubMed Web of Science ®Google Scholar
• Vlahos R, Stambas J, Bozinovski S, Broughton BR, Drummond GR, Selemidis S. Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog. 2011;7(2):e1001271. doi:10.1371/journal.ppat.1001271
   PubMed Web of Science ®Google Scholar
• Vlahos R, Stambas J, Selemidis S. Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy. Trends Pharmacol Sci. 2012;33(1):3–8. doi:10.1016/j.tips.2011.09.001
   PubMed Web of Science ®Google Scholar
• Sarady-Andrews JK, Liu F, Gallo D, et al. Biliverdin administration protects against endotoxin-induced acute lung injury in rats. Am J Physiol Lung Cell Mol Physiol. 2005;289(6):L1131–L1137. doi:10.1152/ajplung.00458.2004
   Web of Science ®Google Scholar
• Pongnimitprasert N, El-Benna J, Foglietti MJ, Gougerot-Pocidalo MA, Bernard M, Braut-Boucher F. Potential role of the “NADPH oxidases” (NOX/DUOX) family in cystic fibrosis. Ann Biol Clin (Paris). 2008;66(6):621–629. doi:10.1684/abc.2008.0285
   Web of Science ®Google Scholar
• McCarty MF Novel prospects for managing cystic fibrosis. Ref Type: Unpublished Work; 2012.
   Google Scholar
• Mao TK, Van de Water J, Gershwin ME. Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients. J Med Food. 2005;8(1):27–30. doi:10.1089/jmf.2005.8.27
   PubMed Web of Science ®Google Scholar
• PentÃn-Rol G, MartÃ-nez-Sánchez G, Cervantes-Llanos M, et al. C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Int Immunopharmacol. 2011;11(1):29–38. doi:10.1016/j.intimp.2010.10.001
   Web of Science ®Google Scholar
• McCarty MF. Clinical potential of phycocyanobilin for induction of T regulatory cells in the management of inflammatory disorders. Med Hypotheses. 2011;77(6):1031–1033. doi:10.1016/j.mehy.2011.08.041
   Web of Science ®Google Scholar
• Basdeo SA, Campbell NK, Sullivan LM, et al. Suppression of human alloreactive TÂ cells by linear tetrapyrroles; relevance for transplantation. Transl Res. 2016;178:81–94. doi:10.1016/j.trsl.2016.07.011
   Web of Science ®Google Scholar
• Gandhi R, Kumar D, Burns EJ, et al. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol. 2010;11(9):846–853. doi:10.1038/ni.1915
   PubMed Web of Science ®Google Scholar
• Phelan D, Winter GM, Rogers WJ, Lam JC, Denison MS. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys. 1998;357(1):155–163. doi:10.1006/abbi.1998.0814
   Web of Science ®Google Scholar
• Vã-tek L. Bilirubin as a signaling molecule. Med Res Rev. 2020;40(4):1335–1351. doi:10.1002/med.21660
   Web of Science ®Google Scholar
• Bindoli A, Rigobello MP. Principles in redox signaling: from chemistry to functional significance. Antioxid Redox Signal. 2013;18(13):1557–1593. doi:10.1089/ars.2012.4655
   PubMed Web of Science ®Google Scholar
• Lo CM, Carroll KS. The redox biochemistry of protein sulfenylation and sulfinylation. J Biol Chem. 2013;288(37):26480–26488. doi:10.1074/jbc.R113.467738
   Web of Science ®Google Scholar
• Dickinson DA, Forman HJ. Glutathione in defense and signaling: lessons from a small thiol. Ann N Y Acad Sci. 2002;973:488–504. doi:10.1111/j.1749-6632.2002.tb04690.x
   PubMed Web of Science ®Google Scholar
• Shelton MD, Chock PB, Mieyal JJ. Glutaredoxin: role in reversible protein s-glutathionylation and regulation of redox signal transduction and protein translocation. Antioxid Redox Signal. 2005;7(3–4):348–366. doi:10.1089/ars.2005.7.348
   PubMed Web of Science ®Google Scholar
• Parsons ZD, Gates KS. Thiol-dependent recovery of catalytic activity from oxidized protein tyrosine phosphatases. Biochemistry. 2013;52(37):6412–6423. doi:10.1021/bi400451m
   Web of Science ®Google Scholar
• Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007;7(4):355–359. doi:10.1016/j.coph.2007.04.005
   PubMed Web of Science ®Google Scholar
• Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. 2008;8(12):1955–1962. doi:10.1517/14728220802517901
   PubMed Web of Science ®Google Scholar
• Blesa S, Cortijo J, Mata M, et al. Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen. Eur Respir J. 2003;21(3):394–400. doi:10.1183/09031936.03.00039602
   Web of Science ®Google Scholar
• Blesa S, Cortijo J, Martinez-Losa M, et al. Effectiveness of oral N -acetylcysteine in a rat experimental model of asthma. Pharmacol Res. 2002;45(2):135–140. doi:10.1006/phrs.2001.0917
   PubMed Web of Science ®Google Scholar
• Eftekhari P, Hajizadeh S, Raoufy MR, et al. Preventive effect of N-acetylcysteine in a mouse model of steroid resistant acute exacerbation of asthma. EXCLI J. 2013;12:184–192.
   PubMed Web of Science ®Google Scholar
• Carlsten C, MacNutt MJ, Zhang Z, Sava F, Pui MM. Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity. Toxicol Sci. 2014;139(2):479–487.
   Web of Science ®Google Scholar
• Aliyali M, Poorhasan AA, Sharifpoor A, Zalli F. Effects of N-acetylcysteine on asthma exacerbation. Iran J Allergy Asthma Immunol. 2010;9(2):103–109.
   Web of Science ®Google Scholar
• Wild AC, Moinova HR, Mulcahy RT. Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem. 1999;274(47):33627–33636. doi:10.1074/jbc.274.47.33627
   PubMed Web of Science ®Google Scholar
• Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004;101(10):3381–3386. doi:10.1073/pnas.0400282101
   PubMed Web of Science ®Google Scholar
• Papanas N, Ziegler D. Efficacy of alpha-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother. 2014;15(18):2721–2731. doi:10.1517/14656566.2014.972935
   PubMed Web of Science ®Google Scholar
• Cho YS, Lee J, Lee TH, et al. Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Allergy Clin Immunol. 2004;114(2):429–435. doi:10.1016/j.jaci.2004.04.004
   PubMed Web of Science ®Google Scholar
• Park SJ, Lee KS, Lee SJ, et al. L-2-Oxothiazolidine-4-carboxylic acid or alpha-lipoic acid attenuates airway remodeling: involvement of nuclear factor-kappaB (NF-kappaB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and hypoxia-inducible factor (HIF). Int J Mol Sci. 2012;13(7):7915–7937. doi:10.3390/ijms13077915
   Web of Science ®Google Scholar
• Lee CC, Wang CC, Huang HM, Lin CL, Leu SJ, Lee YL. Ferulic acid induces Th1 responses by modulating the function of dendritic cells and ameliorates Th2-mediated allergic airway inflammation in mice. Evid Based Complement Alternat Med. 2015;2015:678487. doi:10.1155/2015/678487
   PubMed Web of Science ®Google Scholar
• Sin Singer BA, Carvalho Gouveia AC, de Souza Alves CC, et al. Ferulic acid supresses Th2 immune response and prevents remodeling in ovalbumin-induced pulmonary allergy associated with inhibition of epithelial-derived cytokines. Pulm Pharmacol Ther. 2017;45:202–209. doi:10.1016/j.pupt.2017.07.001
   Web of Science ®Google Scholar
• Alam J, Stewart D, Touchard C, Boinapally S, Choi AM, Cook JL. Nrf2, a Cap’n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 1999;274(37):26071–26078. doi:10.1074/jbc.274.37.26071
   PubMed Web of Science ®Google Scholar
• Allan CB, Lacourciere GM, Stadtman TC. Responsiveness of selenoproteins to dietary selenium. Annu Rev Nutr. 1999;19:1–16. doi:10.1146/annurev.nutr.19.1.1
   PubMed Web of Science ®Google Scholar
• Chen M, Sun Y, Wu Y. Lower circulating zinc and selenium levels are associated with an increased risk of asthma: evidence from a meta-analysis. Public Health Nutr. 2020;23(9):1555–1562. doi:10.1017/S1368980019003021
   Web of Science ®Google Scholar
• Dupont LL, Glynos C, Bracke KR, Brouckaert P, Brusselle GG. Role of the nitric oxide-soluble guanylyl cyclase pathway in obstructive airway diseases. Pulm Pharmacol Ther. 2014;29(1):1–6. doi:10.1016/j.pupt.2014.07.004
   PubMed Web of Science ®Google Scholar
• Ellis JL. Role of soluble guanylyl cyclase in the relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea and human bronchus. J Pharmacol Exp Ther. 1997;280(3):1215–1218.
   Web of Science ®Google Scholar
• Hamad AM, Johnson SR, Knox AJ. Antiproliferative effects of NO and ANP in cultured human airway smooth muscle. Am J Physiol. 1999;277(5 Pt 1):L910–L918. doi:10.1152/ajplung.1999.277.5.L910
   Web of Science ®Google Scholar
• Yu H, Payne TJ, Mohanty DK. Effects of slow, sustained, and rate-tunable nitric oxide donors on human aortic smooth muscle cells proliferation. Chem Biol Drug Des. 2011;78(4):527–534. doi:10.1111/j.1747-0285.2011.01174.x
   Web of Science ®Google Scholar
• Jain B, Rubinstein I, Robbins RA, Leise KL, Sisson JH. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun. 1993;191(1):83–88. doi:10.1006/bbrc.1993.1187
   Web of Science ®Google Scholar
• Tamaoki J, Kondo M, Tagaya E, Takemura K, Konno K. Zizyphi fructus, a constituent of antiasthmatic herbal medicine, stimulates airway epithelial ciliary motility through nitric oxide generation. Exp Lung Res. 1996;22(3):255–266. doi:10.3109/01902149609031774
   PubMed Web of Science ®Google Scholar
• Ten BR, De CR, Van HR, et al. Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in mice. Respir Res. 2006;7:58. doi:10.1186/1465-9921-7-58
   Web of Science ®Google Scholar
• Kobayashi K, Nishimura Y, Yamashita T, Nishiuma T, Satouchi M, Yokoyama M. The effect of overexpression of endothelial nitric oxide synthase on eosinophilic lung inflammation in a murine model. Int Immunopharmacol. 2006;6(7):1040–1052. doi:10.1016/j.intimp.2005.09.016
   Web of Science ®Google Scholar
• Thomazzi SM, Moreira J, Marcondes S, Nucci GD, Antunes E. Role of cyclic GMP on inhibition by nitric oxide donors of human eosinophil chemotaxis in vitro. Br J Pharmacol. 2004;141(4):653–660. doi:10.1038/sj.bjp.0705661
   Web of Science ®Google Scholar
• Baldissera L Jr, Squebola-Cola DM, Calixto MC, et al. The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis. Pulm Pharmacol Ther. 2016;41:86–95. doi:10.1016/j.pupt.2016.11.001
   Web of Science ®Google Scholar
• Tawa M, Shimosato T, Iwasaki H, Imamura T, Okamura T. Effects of peroxynitrite on relaxation through the NO/sGC/cGMP pathway in isolated rat iliac arteries. J Vasc Res. 2014;51(6):439–446. doi:10.1159/000371491
   Web of Science ®Google Scholar
• Milstien S, Katusic Z. Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Biochem Biophys Res Commun. 1999;263(3):681–684. doi:10.1006/bbrc.1999.1422
   PubMed Web of Science ®Google Scholar
• Pope AJ, Druhan L, Guzman JE, et al. Role of DDAH-1 in lipid peroxidation product-mediated inhibition of endothelial NO generation. Am J Physiol Cell Physiol. 2007;293(5):C1679–C1686. doi:10.1152/ajpcell.00224.2007
   Web of Science ®Google Scholar
• McCarty MF. Asymmetric dimethylarginine is a well established mediating risk factor for cardiovascular morbidity and mortality-should patients with elevated levels be supplemented with citrulline? Healthcare (Basel). 2016;4(3):40. doi:10.3390/healthcare4030040
   Google Scholar
• Kinker KG, Gibson AM, Bass SA, et al. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma. PLoS One. 2014;9(1):e85148. doi:10.1371/journal.pone.0085148
   PubMed Web of Science ®Google Scholar
• Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993;6(9):1368–1370.
   PubMed Web of Science ®Google Scholar
• Persson MG, Zetterstrom O, Agrenius V, Ihre E, Gustafsson LE. Single-breath nitric oxide measurements in asthmatic patients and smokers. Lancet. 1994;343(8890):146–147. doi:10.1016/S0140-6736(94)90935-0
   Web of Science ®Google Scholar
• Brindicci C, Ito K, Barnes PJ, Kharitonov SA. Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers. Chest. 2007;132(2):581–588. doi:10.1378/chest.06-3046
   Web of Science ®Google Scholar
• Ansarin K, Chatkin JM, Ferreira IM, Gutierrez CA, Zamel N, Chapman KR. Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function. Eur Respir J. 2001;17(5):934–938. doi:10.1183/09031936.01.17509340
   PubMed Web of Science ®Google Scholar
• Papapetropoulos A, Simoes DC, Xanthou G, Roussos C, Gratziou C. Soluble guanylyl cyclase expression is reduced in allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2006;290(1):L179–L184. doi:10.1152/ajplung.00330.2005
   Web of Science ®Google Scholar
• Placeres-Uray F, De alfonzo RG, Lippo dB I, Alfonzo MJ. Soluble guanylyl cyclase is reduced in airway smooth muscle cells from a murine model of allergic asthma. World Allergy Organ J. 2010;3(12):271–276. doi:10.1097/WOX.0b013e318201d80b
   Google Scholar
• Tajti G, Papp C, Kardos L, et al. Positive correlation of airway resistance and serum asymmetric dimethylarginine (ADMA) in bronchial asthma patients lacking evidence for systemic inflammation. Allergy Asthma Clin Immunol. 2018;14:2. doi:10.1186/s13223-017-0226-5
   Web of Science ®Google Scholar
• Carraro S, Giordano G, Piacentini G, et al. Asymmetric dimethylarginine in exhaled breath condensate and serum of children with asthma. Chest. 2013;144(2):405–410. doi:10.1378/chest.12-2379
   Web of Science ®Google Scholar
• Holguin F, Comhair SA, Hazen SL, et al. An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype. Am J Respir Crit Care Med. 2013;187(2):153–159. doi:10.1164/rccm.201207-1270OC
   PubMed Web of Science ®Google Scholar
• Scott JA, North ML, Rafii M, et al. Asymmetric dimethylarginine is increased in asthma. Am J Respir Crit Care Med. 2011;184(7):779–785. doi:10.1164/rccm.201011-1810OC
   PubMed Web of Science ®Google Scholar
• Holguin F. Arginine and nitric oxide pathways in obesity-associated asthma. J Allergy (Cairo). 2013;2013:714595. doi:10.1155/2013/714595
   PubMedGoogle Scholar
• Waugh WH, Daeschner CW III, Files BA, McConnell ME, Strandjord SE. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. J Natl Med Assoc. 2001;93(10):363–371.
   Web of Science ®Google Scholar
• Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51–59. doi:10.1111/j.1365-2125.2007.02990.x
   PubMed Web of Science ®Google Scholar
• Winnica D, Que LG, Baffi C, et al. l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells. Clin Exp Allergy. 2017;47(2):190–199. doi:10.1111/cea.12802
   PubMed Web of Science ®Google Scholar
• Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev. 2006;24(3–4):275–290. doi:10.1111/j.1527-3466.2006.00275.x
   PubMed Web of Science ®Google Scholar
• Mabalirajan U, Ahmad T, Leishangthem GD, et al. Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma. J Allergy Clin Immunol. 2010;125(3):626–635. doi:10.1016/j.jaci.2009.10.065
   Web of Science ®Google Scholar
• Zhang R, Kubo M, Murakami I, et al. l-Arginine administration attenuates airway inflammation by altering l-arginine metabolism in an NC/Nga mouse model of asthma. J Clin Biochem Nutr. 2015;56(3):201–207. doi:10.3164/jcbn.14-140
   PubMed Web of Science ®Google Scholar
• Al Qadi-Nassar B, Bichon-Laurent F, Portet K, Tramini P, Arnoux B, Michel A. Effects of L-arginine and phosphodiesterase-5 inhibitor, sildenafil, on inflammation and airway responsiveness of sensitized BP2 mice. Fundam Clin Pharmacol. 2007;21(6):611–620. doi:10.1111/j.1472-8206.2007.00523.x
   Web of Science ®Google Scholar
• Arikan-Ayyildiz Z, Karaman M, Firinci F, et al. Effects of inhaled L-arginine administration in a murine model of acute asthma. Iran J Allergy Asthma Immunol. 2014;13(5):317–323.
   PubMed Web of Science ®Google Scholar
• Takano H, Lim HB, Miyabara Y, Ichinose T, Yoshikawa T, Sagai M. Oral administration of L-arginine potentiates allergen-induced airway inflammation and expression of interleukin-5 in mice. J Pharmacol Exp Ther. 1998;286(2):767–771.
   Web of Science ®Google Scholar
• Klein E, Weigel J, Buford MC, Holian A, Wells SM. Asymmetric dimethylarginine potentiates lung inflammation in a mouse model of allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2010;299(6):L816–L825. doi:10.1152/ajplung.00188.2010
   Web of Science ®Google Scholar
• Holguin F, Grasemann H, Sharma S, et al. L-Citrulline increases nitric oxide and improves control in obese asthmatics. JCI Insight. 2019;4(24):e131733. doi:10.1172/jci.insight.131733
   PubMed Web of Science ®Google Scholar
• Asagami T, Abbasi F, Stuelinger M, et al. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism. 2002;51(7):843–846. doi:10.1053/meta.2002.33349
   PubMed Web of Science ®Google Scholar
• Chen CZ, Hsu CH, Li CY, Hsiue TR. 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. doi:10.1080/02770903.2017.1283698
   PubMed Web of Science ®Google Scholar
• Li CY, Erickson SR, Wu CH. Metformin use and asthma outcomes among patients with concurrent asthma and diabetes. Respirology. 2016;21(7):1210–1218. doi:10.1111/resp.12818
   PubMed Web of Science ®Google Scholar
• Li Z, Zheng J, Zhang N, Li C. Berberine improves airway inflammation and inhibits NF-kappaB signaling pathway in an ovalbumin-induced rat model of asthma. J Asthma. 2016;53(10):999–1005. doi:10.1080/02770903.2016.1180530
   PubMed Web of Science ®Google Scholar
• McCarty MF. Oster rediscovered–mega-dose folate for symptomatic atherosclerosis. Med Hypotheses. 2007;69(2):325–332. doi:10.1016/j.mehy.2004.11.049
   PubMed Web of Science ®Google Scholar
• Moens AL, Claeys MJ, Wuyts FL, et al. Effect of folic acid on endothelial function following acute myocardial infarction. Am J Cardiol. 2007;99(4):476–481. doi:10.1016/j.amjcard.2006.08.057
   PubMed Web of Science ®Google Scholar
• Moens AL, Vrints CJ, Claeys MJ, Timmermans JP, Champion HC, Kass DA. Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease. Am J Physiol Heart Circ Physiol. 2008;294(5):H1971–H1977. doi:10.1152/ajpheart.91503.2007
   Web of Science ®Google Scholar
• Tawakol A, Migrino RQ, Aziz KS, et al. High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease. J Am Coll Cardiol. 2005;45(10):1580–1584. doi:10.1016/j.jacc.2005.02.038
   PubMed Web of Science ®Google Scholar
• Rezk BM, Haenen GR, van der Vijgh WJ, Bast A. Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore. FEBS Lett. 2003;555(3):601–605. doi:10.1016/S0014-5793(03)01358-9
   PubMed Web of Science ®Google Scholar
• Crabtree MJ, Hale AB, Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. Free Radic Biol Med. 2011;50(11):1639–1646. doi:10.1016/j.freeradbiomed.2011.03.010
   PubMed Web of Science ®Google Scholar
• Gao L, Siu KL, Chalupsky K, et al. Role of uncoupled endothelial nitric oxide synthase in abdominal aortic aneurysm formation: treatment with folic acid. Hypertension. 2012;59(1):158–166. doi:10.1161/HYPERTENSIONAHA.111.181644
   PubMed Web of Science ®Google Scholar
• Siu KL, Miao XN, Cai H. Recoupling of eNOS with folic acid prevents abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E null mice. PLoS One. 2014;9(2):e88899. doi:10.1371/journal.pone.0088899
   Web of Science ®Google Scholar
• Chalupsky K, Kracun D, Kanchev I, Bertram K, Gorlach A. Folic acid promotes recycling of tetrahydrobiopterin and protects against hypoxia-induced pulmonary hypertension by recoupling endothelial nitric oxide synthase. Antioxid Redox Signal. 2015;23(14):1076–1091. doi:10.1089/ars.2015.6329
   Web of Science ®Google Scholar
• Sharma SK, Ebadi M. Metallothionein attenuates 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in dopaminergic neurons. Antioxid Redox Signal. 2003;5(3):251–264. doi:10.1089/152308603322110832
   PubMed Web of Science ®Google Scholar
• Cai L, Klein JB, Kang YJ. Metallothionein inhibits peroxynitrite-induced DNA and lipoprotein damage. J Biol Chem. 2000;275(50):38957–38960. doi:10.1074/jbc.C000593200
   Web of Science ®Google Scholar
• Inoue K, Takano H, Yanagisawa R, et al. Role of metallothionein in antigen-related airway inflammation. Exp Biol Med (Maywood). 2005;230(1):75–81. doi:10.1177/153537020523000110
   Web of Science ®Google Scholar
• Sullivan VK, Burnett FR, Cousins RJ. Metallothionein expression is increased in monocytes and erythrocytes of young men during zinc supplementation. J Nutr. 1998;128(4):707–713. doi:10.1093/jn/128.4.707
   Web of Science ®Google Scholar
• Cao J, Cousins RJ. Metallothionein mRNA in monocytes and peripheral blood mononuclear cells and in cells from dried blood spots increases after zinc supplementation of men. J Nutr. 2000;130(9):2180–2187. doi:10.1093/jn/130.9.2180
   Web of Science ®Google Scholar
• Rerksuppaphol S, Rerksuppaphol L. Zinc supplementation in children with asthma exacerbation. Pediatr Rep. 2016;8(4):6685. doi:10.4081/pr.2016.6685
   Google Scholar
• Ghaffari J, Khalilian A, Salehifar E, Khorasani E, Rezaii MS. Effect of zinc supplementation in children with asthma: a randomized, placebo-controlled trial in northern Islamic Republic of Iran. East Mediterr Health J. 2014;20(6):391–396. doi:10.26719/2014.20.6.391
   Web of Science ®Google Scholar
• Morgan CI, Ledford JR, Zhou P, Page K. Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen. J Inflamm (Lond). 2011;8:36. doi:10.1186/1476-9255-8-36
   Web of Science ®Google Scholar
• Lang C, Murgia C, Leong M, et al. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol. 2007;292(2):L577–L584. doi:10.1152/ajplung.00280.2006
   Web of Science ®Google Scholar
• Szabo C. Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms and implications. Am J Physiol Cell Physiol. 2017;312(1):C3–C15. doi:10.1152/ajpcell.00282.2016
   PubMed Web of Science ®Google Scholar
• Nalli AD, Bhattacharya S, Wang H, Kendig DM, Grider JR, Murthy KS. Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide. Am J Physiol Gastrointest Liver Physiol. 2017;313(4):G330–G341. doi:10.1152/ajpgi.00161.2017
   Web of Science ®Google Scholar
• Wang P, Zhang G, Wondimu T, Ross B, Wang R. Hydrogen sulfide and asthma. Exp Physiol. 2011;96(9):847–852. doi:10.1113/expphysiol.2011.057448
   PubMed Web of Science ®Google Scholar
• Wu R, Yao WZ, Chen YH, Geng B, Tang CS. [Plasma level of endogenous hydrogen sulfide in patients with acute asthma]. Beijing Da Xue Xue Bao Yi Xue Ban. 2008;40(5):505–508. (Chinese).
   Google Scholar
• Chen YH, Wu R, Geng B, et al. Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma. Cytokine. 2009;45(2):117–123. doi:10.1016/j.cyto.2008.11.009
   PubMed Web of Science ®Google Scholar
• Chen YH, Wang PP, Wang XM, et al. Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung. Cytokine. 2011;53(3):334–341. doi:10.1016/j.cyto.2010.12.006
   PubMed Web of Science ®Google Scholar
• Perry MM, Hui CK, Whiteman M, et al. Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells. Am J Respir Cell Mol Biol. 2011;45(4):746–752. doi:10.1165/rcmb.2010-0304OC
   Web of Science ®Google Scholar
• Roviezzo F, Bertolino A, Sorrentino R, et al. Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation. Pharmacol Res. 2015;100:85–92. doi:10.1016/j.phrs.2015.07.032
   PubMed Web of Science ®Google Scholar
• Rodrigues L, Ekundi-Valentim E, Florenzano J, et al. Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice. Pharmacol Res. 2017;115:255–266. doi:10.1016/j.phrs.2016.11.006
   PubMed Web of Science ®Google Scholar
• Zhang G, Wang P, Yang G, Cao Q, Wang R. The inhibitory role of hydrogen sulfide in airway hyperresponsiveness and inflammation in a mouse model of asthma. Am J Pathol. 2013;182(4):1188–1195. doi:10.1016/j.ajpath.2012.12.008
   Web of Science ®Google Scholar
• DiNicolantonio JJ, OKeefe JH, McCarty MF. Boosting endogenous production of vasoprotective hydrogen sulfide via supplementation with taurine and N-acetylcysteine: a novel way to promote cardiovascular health. Open Heart. 2017;4(1):e000600. doi:10.1136/openhrt-2017-000600
   Web of Science ®Google Scholar
• Sun Q, Wang B, Li Y, et al. Taurine supplementation lowers blood pressure and improves vascular function in prehypertension: randomized, Double-Blind, Placebo-Controlled Study. Hypertension. 2016;67(3):541–549. doi:10.1161/HYPERTENSIONAHA.115.06624
   PubMed Web of Science ®Google Scholar
• Abebe W, Mozaffari MS. Role of taurine in the vasculature: an overview of experimental and human studies. Am J Cardiovasc Dis. 2011;1(3):293–311.
   PubMedGoogle Scholar
• Murakami S. Taurine and atherosclerosis. Amino Acids. 2014;46(1):73–80. doi:10.1007/s00726-012-1432-6
   PubMed Web of Science ®Google Scholar
• Cortijo J, Blesa S, Martinez-Losa M, et al. Effects of taurine on pulmonary responses to antigen in sensitized Brown-Norway rats. Eur J Pharmacol. 2001;431(1):111–117. doi:10.1016/S0014-2999(01)01433-9
   Web of Science ®Google Scholar
• Follmann M, Griebenow N, Hahn MG, et al. The chemistry and biology of soluble guanylate cyclase stimulators and activators. Angew Chem Int Ed Engl. 2013;52(36):9442–9462. doi:10.1002/anie.201302588
   PubMed Web of Science ®Google Scholar
• Nossaman B, Pankey E, Kadowitz P. Stimulators and activators of soluble guanylate cyclase: review and potential therapeutic indications. Crit Care Res Pract. 2012;2012:290805. doi:10.1155/2012/290805
   Google Scholar
• Ghosh A, Koziol-White CJ, Asosingh K, et al. Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma. Proc Natl Acad Sci U S A. 2016;113(17):E2355–E2362. doi:10.1073/pnas.1524398113
   PubMed Web of Science ®Google Scholar
• Koress C, Swan K, Kadowitz P. Soluble guanylate cyclase stimulators and activators: novel therapies for pulmonary vascular disease or a different method of increasing cGMP? Curr Hypertens Rep. 2016;18(5):42. doi:10.1007/s11906-016-0645-6
   PubMed Web of Science ®Google Scholar
• Vesely DL. Biotin enhances guanylate cyclase activity. Science. 1982;216(4552):1329–1330. doi:10.1126/science.6123152
   PubMed Web of Science ®Google Scholar
• Vesely DL, Wormser HC, Abramson HN. Biotin analogs activate guanylate cyclase. Mol Cell Biochem. 1984;60(2):109–114. doi:10.1007/BF00222480
   Web of Science ®Google Scholar
• Singh IN, Dakshinamurti K. Stimulation of guanylate cyclase and RNA polymerase II activities in HeLa cells and fibroblasts by biotin. Mol Cell Biochem. 1988;79(1):47–55. doi:10.1007/BF00229397
   Web of Science ®Google Scholar
• Watanabe-Kamiyama M, Kamiyama S, Horiuchi K, et al. Antihypertensive effect of biotin in stroke-prone spontaneously hypertensive rats. Br J Nutr. 2008;99(4):756–763. doi:10.1017/S0007114507841122
   PubMed Web of Science ®Google Scholar
• McCarty MF. In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control. Med Hypotheses. 2016;95:45–48. doi:10.1016/j.mehy.2016.08.002
   Web of Science ®Google Scholar
• Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: a randomised, double-blind, placebo-controlled study. Mult Scler. 2016;22(13):1719–1731. doi:10.1177/1352458516667568
   PubMed Web of Science ®Google Scholar
• McCarty MF, DiNicolantonio JJ. Neuroprotective potential of high-dose biotin. Med Hypotheses. 2017;109:145–149. doi:10.1016/j.mehy.2017.10.012
   PubMed Web of Science ®Google Scholar
• Mock DM. Biotin: from Nutrition to Therapeutics. J Nutr. 2017;147(8):1487–1492. doi:10.3945/jn.116.238956
   PubMed Web of Science ®Google Scholar
• Zhong Z, Wheeler MD, Li X, et al. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care. 2003;6(2):229–240. doi:10.1097/00075197-200303000-00013
   PubMed Web of Science ®Google Scholar
• McCarty MF, DiNicolantonio JJ. The cardiometabolic benefits of glycine: is glycine an ‘antidote’ to dietary fructose? Open Heart. 2014;1(1):e000103. doi:10.1136/openhrt-2014-000103
   Google Scholar
• Wheeler MD, Rose ML, Yamashima S, et al. Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Am J Physiol Lung Cell Mol Physiol. 2000;279(2):L390–L398. doi:10.1152/ajplung.2000.279.2.L390
   Web of Science ®Google Scholar
• Froh M, Thurman RG, Wheeler MD. Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes. Am J Physiol Gastrointest Liver Physiol. 2002;283(4):G856–G863. doi:10.1152/ajpgi.00503.2001
   Web of Science ®Google Scholar
• Yim PD, Gallos G, Xu D, Zhang Y, Emala CW. Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. FASEB J. 2011;25(5):1706–1717. doi:10.1096/fj.10-170530
   Web of Science ®Google Scholar
• Vargas MH, Del-Razo-Rodriguez R, Lopez-Garcia A, et al. Effect of oral glycine on the clinical, spirometric and inflammatory status in subjects with cystic fibrosis: a pilot randomized trial. BMC Pulm Med. 2017;17(1):206. doi:10.1186/s12890-017-0528-x
   Web of Science ®Google Scholar
• Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr. 2011;94(3):847–853. doi:10.3945/ajcn.110.003483
   PubMed Web of Science ®Google Scholar
• Britton J, Pavord I, Richards K, et al. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample. Lancet. 1994;344(8919):357–362. doi:10.1016/S0140-6736(94)91399-4
   PubMed Web of Science ®Google Scholar
• Hill J, Micklewright A, Lewis S, Britton J. Investigation of the effect of short-term change in dietary magnesium intake in asthma. Eur Respir J. 1997;10(10):2225–2229. doi:10.1183/09031936.97.10102225
   PubMed Web of Science ®Google Scholar
• Kazaks AG, Uriu-Adams JY, Albertson TE, Shenoy SF, Stern JS. Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial. J Asthma. 2010;47(1):83–92. doi:10.3109/02770900903331127
   PubMed Web of Science ®Google Scholar
• Gontijo-Amaral C, Ribeiro MA, Gontijo LS, Condino-Neto A, Ribeiro JD. Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial. Eur J Clin Nutr. 2007;61(1):54–60. doi:10.1038/sj.ejcn.1602475
   Web of Science ®Google Scholar
• Bede O, Nagy D, Suranyi A, Horvath I, Szlavik M, Gyurkovits K. Effects of magnesium supplementation on the glutathione redox system in atopic asthmatic children. Inflamm Res. 2008;57(6):279–286. doi:10.1007/s00011-007-7077-3
   Web of Science ®Google Scholar
• Malmendal A, Linse S, Evenas J, Forsen S, Drakenberg T. Battle for the EF-hands: magnesium-calcium interference in calmodulin. Biochemistry. 1999;38(36):11844–11850. doi:10.1021/bi9909288
   PubMed Web of Science ®Google Scholar
• Grabarek Z. Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins. Biochim Biophys Acta. 2011;1813(5):913–921. doi:10.1016/j.bbamcr.2011.01.017
   Web of Science ®Google Scholar
• Ohki S, Ikura M, Zhang M. Identification of Mg2+-binding sites and the role of Mg2+ on target recognition by calmodulin. Biochemistry. 1997;36(14):4309–4316. doi:10.1021/bi962759m
   Web of Science ®Google Scholar