Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models

1. Kalogeris T, Bao Y, Korthuis RJ. Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol. 2014;2:702–14. doi: 10.1016/j.redox.2014.05.006 24944913

2. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459–544. doi: 10.1016/S0140-6736(16)31012-1 27733281

3. Smith CJ, Denes A, Tyrrell PJ, Di Napoli M. Phase II anti-inflammatory and immune-modulating drugs for acute ischaemic stroke. Expert Opin Investig Drugs. 2015;24:623–43. doi: 10.1517/13543784.2015.1020110 25727670

4. Rossello X, Yellon DM. A critical review on the translational journey of cardioprotective therapies! Int J Cardiol. 2016;220:176–84. doi: 10.1016/j.ijcard.2016.06.131 27379920

5. Blackstone E, Morrison M, Roth MB. H2S induces a suspended animation—like state in mice. Science. 2005;308:518. doi: 10.1126/science.1108581 15845845

6. Cooper CE, Brown GC. The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. J Bioenerg Biomembr. 2008;40:533–9. doi: 10.1007/s10863-008-9166-6 18839291

7. Liu Y-H, Lu M, Hu L-F, Wong PT-H, Webb GD, Bian J-S. Hydrogen sulfide in the mammalian cardiovascular system. Antioxid Redox Signal. 2012;17:141–85. doi: 10.1089/ars.2011.4005 22304473

8. Morrison ML, Blackwood JE, Lockett SL, Iwata A, Winn RK, Roth MB. Surviving blood loss using hydrogen sulfide. J Trauma. 2008;65:183–8. doi: 10.1097/TA.0b013e3181507579 18580516

9. Blackstone E, Roth MB. Suspended animation-like state protects mice from lethal hypoxia. Shock. 2007;27:370–2. doi: 10.1097/SHK.0b013e31802e27a0 17414418

10. Haouzi P, Notet V, Chenuel B, Chalon B, Sponne I, Ogier V, et al. H2S induced hypometabolism in mice is missing in sedated sheep. Respir Physiol Neurobiol. 2008;160:109–15. doi: 10.1016/j.resp.2007.09.001 17980679

11. Simon F, Giudici R, Duy CN, Schelzig H, Öter S, Gröger M, et al. Hemodynamic and metabolic effects of hydrogen sulfide during porcine ischemia/reperfusion injury. Shock. 2008;30:359–64. doi: 10.1097/SHK.0b013e3181674185 18323742

12. Reduction of ischemia-reperfusion mediated cardiac injury in subjects undergoing coronary artery bypass graft surgery. NCT00858936. ClinicalTrials.gov; 2016 [cited 2017 Feb 7]. https://clinicaltrials.gov/ct2/show/NCT00858936?term=IK-1001&rank=2.

13. Wu D, Wang J, Li H, Xue M, Ji A, Li Y. Role of hydrogen sulfide in ischemia-reperfusion injury. Oxid Med Cell Longev. 2015;2015:186908. doi: 10.1155/2015/186908 26064416

14. Berzelius JJ. Ueber die Schwefelsalze. Ann Phys. 1826;83:137–58. doi: 10.1002/andp.18260830602

15. Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, et al. Treatment of Wilson’s disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res. 2009;154:70–7. doi: 10.1016/j.trsl.2009.05.002 19595438

16. Gooneratne SR, Howell JM, Gawthorne JM. Intravenous administration of thiomolybdate for the prevention and treatment of chronic copper poisoning in sheep. Br J Nutr. 1981;46:457–67. 7317341

17. Okada M, Fujikawa Y, Shimizu N, Yamaguchi Y, Kato N, Suzuki K, et al. Decoppering effect of tetrathiomolybdate in the patients with Wilson disease. Biomed Res Trace Elements. 1998;9:155–6.

18. Brewer GJ. The use of copper-lowering therapy with tetrathiomolybdate in medicine. Expert Opin Investig Drugs. 2009;18:89–97. doi: 10.1517/13543780802621859 19053885

19. Dyson A, Moore K, Mongardon N, Andreeva L, Martin J, Singer M. Metabolic modulation by tetrathiomolybdate, a slow-release sulphide donor. Abstracts of the ESICM (European Society of Intensive Care Medicine) 25th Annual Congress. Lisbon, Portugal. October 13–17, 2012. Intensive Care Med. 2012;38(Suppl 1):S8–327.

20. Zolfaghari PS, Pinto BB, Dyson A, Singer M. The metabolic phenotype of rodent sepsis: cause for concern? Intensive Care Med Exp. 2013;1:25. doi: 10.1186/2197-425X-1-6 26266794

21. Wintner EA, Deckwerth TL, Langston W, Bengtsson A, Leviten D, Hill P, et al. A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. Br J Pharmacol. 2010;160:941–57. doi: 10.1111/j.1476-5381.2010.00704.x 20590590

22. Shen X, Pattillo CB, Pardue S, Bir SC, Wang R, Kevil CG. Measurement of plasma hydrogen sulfide in vivo and in vitro. Free Radic Biol Med. 2011;50:1021–31. doi: 10.1016/j.freeradbiomed.2011.01.025 21276849

23. Dagur PK, McCoy JP. Collection, storage, and preparation of human blood cells: handling, storage, and preparation of human blood cells. In: Robinson JP, Darzynkiewicz Z, Hoffman R, Nolan JP, Rabinovitch PS, Watkins S, editors. Current protocols in cytometry. Hoboken (New Jersey): John Wiley & Sons; 2015. pp. 5.1.1–16.

24. Mukhopadhyay P, Rajesh M, Haskó G, Hawkins BJ, Madesh M, Pacher P. Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy. Nat Protoc. 2007;2:2295–301. doi: 10.1038/nprot.2007.327 17853886

25. Moore PK, Whiteman M, editors. Chemistry, biochemistry and pharmacology of hydrogen sulfide. Handbook of experimental pharmacology. Volume 230. Cham (Switzerland): Springer International Publishing; 2015. pp. 337–63.

26. Li L, Whiteman M, Guan YY, Neo KL, Cheng Y, Lee SW, et al. Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation. 2008;117:2351–60. doi: 10.1161/CIRCULATIONAHA.107.753467 18443240

27. Rossoni G, Sparatore A, Tazzari V, Manfredi B, Del Soldato P, Berti F. The hydrogen sulphide-releasing derivative of diclofenac protects against ischaemia-reperfusion injury in the isolated rabbit heart. Br J Pharmacol. 2008;153:100–9. doi: 10.1038/sj.bjp.0707540 17965734

28. Kang J, Li Z, Organ CL, Park C-M, Yang C, Pacheco A, et al. pH-controlled hydrogen sulfide release for myocardial ischemia-reperfusion injury. J Am Chem Soc. 2016;138:6336–9. doi: 10.1021/jacs.6b01373 27172143

29. Park C-M, Zhao Y, Zhu Z, Pacheco A, Peng B, Devarie-Baez NO, et al. Synthesis and evaluation of phosphorodithioate-based hydrogen sulfide donors. Mol Biosyst. 2013;9:2430–6. doi: 10.1039/c3mb70145j 23917226

30. Zhao Y, Bhushan S, Yang C, Otsuka H, Stein JD, Pacheco A, et al. Controllable hydrogen sulfide donors and their activity against myocardial ischemia-reperfusion injury. ACS Chem Biol. 2013;8:1283–90. doi: 10.1021/cb400090d 23547844

31. Zhao Y, Kang J, Park C-M, Bagdon PE, Peng B, Xian M. Thiol-activated gem-dithiols: a new class of controllable hydrogen sulfide donors. Org Lett. 2014;16:4536–9. doi: 10.1021/ol502088m 25141097

32. Zhao Y, Wang H, Xian M. Cysteine-activated hydrogen sulfide (H2S) donors. J Am Chem Soc. 2011;133:15–7. doi: 10.1021/ja1085723 21142018

33. Zhao Y, Yang C, Organ C, Li Z, Bhushan S, Otsuka H, et al. Design, synthesis, and cardioprotective effects of N-mercapto-based hydrogen sulfide donors. J Med Chem. 2015;58:7501–11. doi: 10.1021/acs.jmedchem.5b01033 26317692

34. Weber KM, Leaver DD, Wedd AG. The behaviour of thiomolybdates in in vitro systems. Br J Nutr. 1979;41:403–5. 34421

35. Quagraine E, Georgakaki I, Coucouvanis D. Reactivity and kinetic studies of (NH4)2(MoS4) in acidic aqueous solution: possible relevance to the angiostatic function of the MoS42− ligand. J Inorg Biochem. 2009;103:143–55. doi: 10.1016/j.jinorgbio.2008.09.015 19026449

36. Lowndes SA, Adams A, Timms A, Fisher N, Smythe J, Watt SM, et al. Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors. Clin Cancer Res. 2008;14:7526–34. doi: 10.1158/1078-0432.CCR-08-0315 19010871

37. Xu S, Yang C-T, Meng F-H, Pacheco A, Chen L, Xian M. Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor. Bioorg Med Chem Lett. 2016;26:1585–8. doi: 10.1016/j.bmcl.2016.02.005 26898812

38. Szabo C. Gaseotransmitters: new frontiers for translational science. Sci Transl Med. 2010;2:59ps54. doi: 10.1126/scitranslmed.3000721 21106939

39. Módis K, Bos EM, Calzia E, van Goor H, Coletta C, Papapetropoulos A, et al. Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part II. Pathophysiological and therapeutic aspects: pathophysiology of H2S and mitochondrial function. Br J Pharmacol. 2014;171:2123–46.

40. Kim KK, Abelman S, Yano N, Ribeiro JR, Singh RK, Tipping M, et al. Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1α in cancer cells. Sci Rep. 2015;5:14296. doi: 10.1038/srep14296 26469226

41. Dyson A, Singer M. Tissue oxygen tension monitoring: will it fill the void? Curr Opin Crit Care. 2011;17:281–9. doi: 10.1097/MCC.0b013e328344f1dc 21358405

42. Efficacy and safety study of WTX101 in adult Wilson disease patients. NCT02273596. ClinicalTrials.gov; 2016 [cited 2017 Feb 7]. https://clinicaltrials.gov/ct2/show/NCT02273596.

43. Alvarez HM, Xue Y, Robinson CD, Canalizo-Hernandez MA, Marvin RG, Kelly RA, et al. Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. Science. 2010;327:331–4. doi: 10.1126/science.1179907 19965379

44. Bassindale T, Hosking M. Deaths in Rotorua’s geothermal hot pools: hydrogen sulphide poisoning. Forensic Sci Int. 2011;207:e28–9. doi: 10.1016/j.forsciint.2010.11.025 21183297

45. Burnett WW, King EG, Grace M, Hall WF. Hydrogen sulfide poisoning: review of 5 years’ experience. Can Med Assoc J. 1977;117:1277–80. 144553

46. Petersen LC. The effect of inhibitors on the oxygen kinetics of cytochrome c oxidase. Biochim Biophys Acta. 1977;460:299–307. 192290

47. Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci U S A. 2007;104:15560–5. doi: 10.1073/pnas.0705891104 17878306

48. Kimura H, Nagai Y, Umemura K, Kimura Y. Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxid Redox Signal. 2005;7:795–803. doi: 10.1089/ars.2005.7.795 15890027

49. Zhu H, He M, Bannenberg GL, Moldéus P, Shertzer HG. Effects of glutathione and pH on the oxidation of biomarkers of cellular oxidative stress. Arch Toxicol. 1996;70:628–34. 8870955

50. Campolo M, Esposito E, Ahmad A, Di Paola R, Paterniti I, Cordaro M, et al. Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice. J Neuroinflammation. 2014;11:196. doi: 10.1186/s12974-014-0196-1 25472548

51. Zhang M, Shan H, Chang P, Wang T, Dong W, Chen X, et al. Hydrogen sulfide offers neuroprotection on traumatic brain injury in parallel with reduced apoptosis and autophagy in mice. PLoS ONE. 2014;9:e87241. doi: 10.1371/journal.pone.0087241 24466346

52. Liu C, Pan J, Li S, Zhao Y, Wu LY, Berkman CE, et al. Capture and visualization of hydrogen sulfide by a fluorescent probe. Angew Chem Int Ed Engl. 2011;50:10327–9. doi: 10.1002/anie.201104305 21898737

53. Liu K, Zhang S. Design and characterization of 3-azidothalidomide as a selective hydrogen sulfide probe. Tetrahedron Lett. 2014;55:5566–9. doi: 10.1016/j.tetlet.2014.08.064 25221360

54. Testori C, Holzer M, Sterz F, Stratil P, Hartner Z, Moscato F, et al. Rapid induction of mild therapeutic hypothermia by extracorporeal veno-venous blood cooling in humans. Resuscitation. 2013;84:1051–5. doi: 10.1016/j.resuscitation.2013.03.013 23537698

55. Gotberg M, Olivecrona GK, Koul S, Carlsson M, Engblom H, Ugander M, et al. A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction. Circ Cardiovasc Interv. 2010;3:400–7. doi: 10.1161/CIRCINTERVENTIONS.110.957902 20736446

56. Erlinge D, Götberg M, Lang I, Holzer M, Noc M, Clemmensen P, et al. Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol. 2014;63:1857–65. doi: 10.1016/j.jacc.2013.12.027 24509284