Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras

Abe, 1996, The possible role of hydrogen sulfide as an endogenous neuromodulator, J Neurosci, 16, 1066, 10.1523/JNEUROSCI.16-03-01066.1996 Hughes, 2009, Making and working with hydrogen sulfide: The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: a review, Free Radic Biol Med, 47, 1346, 10.1016/j.freeradbiomed.2009.09.018 Olson, 2011, The therapeutic potential of hydrogen sulfide: separating hype from hope, Am J Physiol Regul Integr Comp Physiol, 301, R297, 10.1152/ajpregu.00045.2011 Chen, 1972, Oxidation of sulfide by O2: catalysis and inhibition, J Sanit Eng Div, 98, 215, 10.1061/JSEDAI.0001372 DeLeon, 2012, Passive loss of hydrogen sulfide in biological experiments, Anal Biochem, 421, 203, 10.1016/j.ab.2011.10.016 Shen, 2011, Measurement of plasma hydrogen sulfide in vivo and in vitro, Free Radic Biol Med, 50, 1021, 10.1016/j.freeradbiomed.2011.01.025 Wintner, 2010, A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood, Br J Pharmacol, 160, 941, 10.1111/j.1476-5381.2010.00704.x Furne, 2008, Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values, Am J Physiol Regul Integr Comp Physiol, 295, R1479, 10.1152/ajpregu.90566.2008 Levitt, 2011, Free and acid-labile hydrogen sulfide concentrations in mouse tissues: anomalously high free hydrogen sulfide in aortic tissue, Antioxid Redox Signal, 15, 373, 10.1089/ars.2010.3525 Whitfield, 2008, Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling, Am J Physiol Regul Integr Comp Physiol, 294, R1930, 10.1152/ajpregu.00025.2008 Olson, 2009, Is hydrogen sulfide a circulating gasotransmitter in vertebrate blood, Biochim Biophys Acta, 1787, 856, 10.1016/j.bbabio.2009.03.019 Ubuka, 2002, Assay methods and biological roles of labile sulfur in animal tissues, J Chromatogr B Analyt Technol Biomed Life Sci, 781, 227, 10.1016/S1570-0232(02)00623-2 Olson, 2010, Hydrogen sulfide and oxygen sensing in the cardiovascular system, Antioxid Redox Signal, 12, 1219, 10.1089/ars.2009.2921 Wu, 2006, Using carbon nanotubes to absorb low-concentration hydrogen sulfide in fluid, IEEE Trans Nanobioscience, 5, 204, 10.1109/TNB.2006.880843 Lippert, 2011, Reaction-based fluorescent probes for selective imaging of hydrogen sulfide in living cells, J Am Chem Soc, 133, 10078, 10.1021/ja203661j Stipanuk, 2004, Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine, Annu Rev Nutr, 24, 539, 10.1146/annurev.nutr.24.012003.132418 Mikami, 2011, Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide, Biochem J, 439, 479, 10.1042/BJ20110841 Ishigami, 2009, A source of hydrogen sulfide and a mechanism of its release in the brain, Antioxid Redox Signal, 11, 205, 10.1089/ars.2008.2132 Shibuya, 2009, 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain, Antioxid Redox Signal, 11, 703, 10.1089/ars.2008.2253 Chiku, 2009, H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia, J Biol Chem, 284, 11601, 10.1074/jbc.M808026200 Kabil, 2010, Redox biochemistry of hydrogen sulfide, J Biol Chem, 285, 21903, 10.1074/jbc.R110.128363 Singh, 2009, Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions, J Biol Chem, 284, 22457, 10.1074/jbc.M109.010868 Stipanuk, 2011, Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur, J Inherit Metab Dis, 34, 17, 10.1007/s10545-009-9006-9 Yuan, 2011, Thiol metabolomics of endothelial cells using capillary liquid chromatography mass spectrometry with isotope coded affinity tags, J Chromatogr A, 1218, 2561, 10.1016/j.chroma.2011.02.063 Kamoun, 2004, Endogenous production of hydrogen sulfide in mammals, Amino Acids, 26, 243, 10.1007/s00726-004-0072-x Kimura, 2011, Hydrogen sulfide: its production, release and functions, Amino Acids, 41, 113, 10.1007/s00726-010-0510-x Olson, 2010, Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism, Am J Physiol Regul Integr Comp Physiol, 298, R51, 10.1152/ajpregu.00576.2009 Whiteman, 2011, Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools, Clin Sci (Lond), 121, 459, 10.1042/CS20110267 Kabil, 2011, The quantitative significance of the transsulfuration enzymes for H2S production in murine tissues, Antioxid Redox Signal, 15, 363, 10.1089/ars.2010.3781 Bearden, 2010, Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress, Am J Physiol Heart Circ Physiol, 299, H1568, 10.1152/ajpheart.00555.2010 Banerjee, 2005, Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a PLP-dependent hemesensor protein, Arch Biochem Biophys, 433, 144, 10.1016/j.abb.2004.08.037 Mikami, 2011, Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx, J Biol Chem, 286, 39379, 10.1074/jbc.M111.298208 Szabo, 2007, Hydrogen sulphide and its therapeutic potential, Nat Rev Drug Discov, 6, 917, 10.1038/nrd2425 Julian, 2002, Enzymatic hydrogen sulfide production in marine invertebrate tissues, Comp Biochem Physiol A Mol Integr Physiol, 133, 105, 10.1016/S1095-6433(02)00122-8 Liang, 2011, Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats, Lab Invest, 91, 12, 10.1038/labinvest.2010.156 Yu, 1998, Sodium hydrosulfite contractions of smooth muscle are calcium and myosin phosphorylation independent, Am J Physiol, 275, L976 Wetzelberger, 2010, Postischemic deactivation of cardiac aldose reductase: role of glutathione S-transferase P and glutaredoxin in regeneration of reduced thiols from sulfenic acids, J Biol Chem, 285, 26135, 10.1074/jbc.M110.146423 Hildebrandt, 2008, Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria, FEBS J, 275, 3352, 10.1111/j.1742-4658.2008.06482.x Lagoutte, 2010, Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes, Biochim Biophys Acta, 1797, 1500, 10.1016/j.bbabio.2010.04.004 Bouillaud, 2011, Mitochondria and sulfide: a very old story of poisoning, feeding, and signaling, Antioxid Redox Signal, 15, 379, 10.1089/ars.2010.3678 Hildebrandt, 2011, Modulation of sulfide oxidation and toxicity in rat mitochondria by dehydroascorbic acid, Biochim Biophys Acta, 1807, 1206, 10.1016/j.bbabio.2011.06.003 Caliendo, 2010, Synthesis and biological effects of hydrogen sulfide (H2S): development of H2S-releasing drugs as pharmaceuticals, J Med Chem, 53, 6275, 10.1021/jm901638j Fiorucci, 2011, Hydrogen sulfide-based therapies: focus on H2S releasing NSAIDs, Inflamm Allergy Drug Targets, 10, 133, 10.2174/187152811794776213 Martelli, 2010, Hydrogen sulphide: novel opportunity for drug discovery, Med Res Rev Bannenberg, 2009, Therapeutic applications of the gaseous mediators carbon monoxide and hydrogen sulfide, Expert Opin Ther Pat, 19, 663, 10.1517/13543770902858824 Gong, 2011, A new hope for neurodegeneration: possible role of hydrogen sulfide, J Alzheimers Dis, 24, 173, 10.3233/JAD-2011-110128 Kimura, 2010, Hydrogen sulfide: from brain to gut, Antioxid Redox Signal, 12, 1111, 10.1089/ars.2009.2919 King, 2011, Cytoprotective actions of hydrogen sulfide in ischaemia-reperfusion injury, Exp Physiol, 96, 840, 10.1113/expphysiol.2011.059725 Li, 2011, Hydrogen sulfide and cell signaling, Annu Rev Pharmacol Toxicol, 51, 169, 10.1146/annurev-pharmtox-010510-100505 Liu, 2011, Leonurine-cysteine analog conjugates as a new class of multifunctional anti-myocardial ischemia agent, Eur J Med Chem, 46, 3996, 10.1016/j.ejmech.2011.05.073 Tan, 2010, Hydrogen sulfide: a novel signaling molecule in the central nervous system, Neurochem Int, 56, 3, 10.1016/j.neuint.2009.08.008 Whiteman, 2011, Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising, Expert Rev Clin Pharmacol, 4, 13, 10.1586/ecp.10.134 Derwall, 2011, Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: a proof of concept study on metabolic and vasomotor effects, Crit Care, 15, R51, 10.1186/cc10016 Insko, 2009, Detection of exhaled hydrogen sulphide gas in rats exposed to intravenous sodium sulphide, Br J Pharmacol, 157, 944, 10.1111/j.1476-5381.2009.00248.x Toombs, 2010, Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide, Br J Clin Pharmacol, 69, 626, 10.1111/j.1365-2125.2010.03636.x Kaschula, 2011, Anti-proliferation activity of synthetic ajoene analogues on cancer cell-lines, Anticancer Agents Med Chem, 11, 260, 10.2174/187152011795347450 Benavides, 2007, Hydrogen sulfide mediates the vasoactivity of garlic, Proc Natl Acad Sci USA, 104, 17977, 10.1073/pnas.0705710104 Sener, 2007, Role of garlic in the prevention of ischemia-reperfusion injury, Mol Nutr Food Res, 51, 1345, 10.1002/mnfr.200700078 Tsubura, 2011, Anticancer effects of garlic and garlic-derived compounds for breast cancer control, Anticancer Agents Med Chem, 11, 249, 10.2174/187152011795347441 Padiya, 2011, Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats, Nutr Metab (Lond), 8, 53, 10.1186/1743-7075-8-53 Ye, 2002, Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans, Clin Chim Acta, 316, 43, 10.1016/S0009-8981(01)00727-6 Jackson, 2007, Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization, Vascul Pharmacol, 46, 77, 10.1016/j.vph.2006.06.015 Shan, 2010, Protective effect of sulforaphane on human vascular endothelial cells against lipopolysaccharide-induced inflammatory damage, Cardiovasc Toxicol, 10, 139, 10.1007/s12012-010-9072-0 Zhu, 2008, Potent induction of total cellular and mitochondrial antioxidants and phase 2 enzymes by cruciferous sulforaphane in rat aortic smooth muscle cells: cytoprotection against oxidative and electrophilic stress, Cardiovasc Toxicol, 8, 115, 10.1007/s12012-008-9020-4 Mukherjee, 2010, Comparison of the protective effects of steamed and cooked broccolis on ischaemia-reperfusion-induced cardiac injury, Br J Nutr, 103, 815, 10.1017/S0007114509992492 Calabrese, 2010, Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders, Antioxid Redox Signal, 13, 1763, 10.1089/ars.2009.3074 Li, 2008, Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide, Circulation, 117, 2351, 10.1161/CIRCULATIONAHA.107.753467 Lee, 2011, The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo, PLoS One, 6, e21077, 10.1371/journal.pone.0021077 Yu, 2010, [Effect of synthesized GYY4137, a slowly releasing hydrogen sulfide donor, on cell viability and distribution of hydrogen sulfide in mice], Beijing Da Xue Xue Bao, 42, 493 Yong, 2011, Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide, Antioxid Redox Signal, 14, 2081, 10.1089/ars.2010.3572 Li, 2009, GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat, Free Radic Biol Med, 47, 103, 10.1016/j.freeradbiomed.2009.04.014 Wallace, 2007, Hydrogen sulfide enhances ulcer healing in rats, FASEB J, 21, 4070, 10.1096/fj.07-8669com Wang, 2010, Protective effects of cysteine analogues on acute myocardial ischemia: novel modulators of endogenous H(2)S production, Antioxid Redox Signal, 12, 1155, 10.1089/ars.2009.2947 Gong, 2011, S-propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuates lipopolysaccharide-induced spatial learning and memory impairment: involvement of TNF signaling and NF-kappaB pathway in rats, Brain Behav Immun, 25, 110, 10.1016/j.bbi.2010.09.001 Chuah, 2007, S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway, Am J Physiol Heart Circ Physiol, 293, H2693, 10.1152/ajpheart.00853.2007 Liu, 2010, Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents, Bioorg Med Chem Lett, 20, 6942, 10.1016/j.bmcl.2010.09.135 Ma, 2011, H2S donor, S-propargyl-cysteine, increases CSE in SGC-7901 and cancer-induced mice: evidence for a novel anti-cancer effect of endogenous H2S?, PLoS One, 6, e20525, 10.1371/journal.pone.0020525 Pan, 2011, S-Propargyl-cysteine (SPRC) attenuated lipopolysaccharide-induced inflammatory response in H9c2 cells involved in a hydrogen sulfide-dependent mechanism, Amino Acids, 41, 205, 10.1007/s00726-011-0834-1 Toohey, 2009, Sulfur metabolism in AIDS: cystamine as an anti-HIV agent, AIDS Res Hum Retroviruses, 25, 1057, 10.1089/aid.2009.0091 Toohey, 1986, Persulfide sulfur is a growth factor for cells defective in sulfur metabolism, Biochem Cell Biol, 64, 758, 10.1139/o86-103 Zhao, 2011, Cysteine-activated hydrogen sulfide (H2S) donors, J Am Chem Soc, 133, 15, 10.1021/ja1085723 Lee, 2010, Effects of hydrogen sulfide-releasing L-DOPA derivatives on glial activation: potential for treating Parkinson disease, J Biol Chem, 285, 17318, 10.1074/jbc.M110.115261 Sparatore, 2009, Pharmacological profile of a novel H(2)S-releasing aspirin, Free Radic Biol Med, 46, 586, 10.1016/j.freeradbiomed.2008.11.013 Giustarini, 2010, Modulation of thiol homeostasis induced by H2S-releasing aspirin, Free Radic Biol Med, 48, 1263, 10.1016/j.freeradbiomed.2010.02.014 Lee, 2010, Hydrogen sulfide-releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation, Glia, 58, 103, 10.1002/glia.20905 Muzaffar, 2008, H2S-donating sildenafil (ACS6) inhibits superoxide formation and gp91phox expression in arterial endothelial cells: role of protein kinases A and G, Br J Pharmacol, 155, 984, 10.1038/bjp.2008.326 Li, 2007, Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative, Free Radic Biol Med, 42, 706, 10.1016/j.freeradbiomed.2006.12.011 Lazzarato, 2011, New nitric oxide or hydrogen sulfide releasing aspirins, J Med Chem, 54, 5478, 10.1021/jm2004514 Rossoni, 2010, Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological cardiovascular alterations induced by glutathione depletion in rats, Eur J Pharmacol, 648, 139, 10.1016/j.ejphar.2010.08.039 Shukla, 2009, Effect of hydrogen sulphide-donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats, BJU Int, 103, 1522, 10.1111/j.1464-410X.2009.08415.x Rossoni, 2008, The hydrogen sulphide-releasing derivative of diclofenac protects against ischaemia-reperfusion injury in the isolated rabbit heart, Br J Pharmacol, 153, 100, 10.1038/sj.bjp.0707540 Baskar, 2008, Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative inhibit rat vascular smooth muscle cell proliferation, Eur J Pharmacol, 594, 1, 10.1016/j.ejphar.2008.07.029 Liu, 2011, ACS84, a novel hydrogen sulfide-releasing compound, protects against amyloid beta-induced cell cytotoxicity, Neurochem Int, 58, 591, 10.1016/j.neuint.2011.01.023 Liu, 2011, H2S releasing aspirin protects amyloid beta induced cell toxicity in BV-2 microglial cells, Neuroscience, 193, 80, 10.1016/j.neuroscience.2011.07.023 Bhatia, 2005, Hydrogen sulphide is a mediator of carrageenan-induced hindpaw oedema in the rat, Br J Pharmacol, 145, 141, 10.1038/sj.bjp.0706186 Li, 2005, Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse, Faseb J, 19, 1196, 10.1096/fj.04-3583fje Anuar, 2006, Flurbiprofen and its nitric oxide-releasing derivative protect against septic shock in rats, Inflamm Res, 55, 498, 10.1007/s00011-006-5150-y Anuar, 2006, Nitric oxide-releasing flurbiprofen reduces formation of proinflammatory hydrogen sulfide in lipopolysaccharide-treated rat, Br J Pharmacol, 147, 966, 10.1038/sj.bjp.0706696 Bhatia, 2005, Role of hydrogen sulfide in acute pancreatitis and associated lung injury, Faseb J, 19, 623, 10.1096/fj.04-3023fje Tamizhselvi, 2007, Hydrogen sulfide acts as a mediator of inflammation in acute pancreatitis: in vitro studies using isolated mouse pancreatic acinar cells, J Cell Mol Med, 11, 315, 10.1111/j.1582-4934.2007.00024.x Zanardo, 2006, Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation, Faseb J, 20, 2118, 10.1096/fj.06-6270fje Mariggio, 1998, Sulfide enhancement of PMN apoptosis, Immunopharmacol Immunotoxicol, 20, 399, 10.3109/08923979809034822 Gilroy, 2004, Inflammatory resolution: new opportunities for drug discovery, Nat Rev Drug Discov, 3, 401, 10.1038/nrd1383 Bjorkman, 1999, Current status of nonsteroidal anti-inflammatory drug (NSAID) use in the United States: risk factors and frequency of complications, Am J Med, 107, 3S, 10.1016/S0002-9343(99)00362-9 Wallace, 2008, Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself, Physiol Rev, 88, 1547, 10.1152/physrev.00004.2008 Okabe, 2005, An overview of acetic acid ulcer models--the history and state of the art of peptic ulcer research, Biol Pharm Bull, 28, 1321, 10.1248/bpb.28.1321 Wallace, 2007, Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat, Gastroenterology, 132, 261, 10.1053/j.gastro.2006.11.042 Wallace, 2007, Hydrogen sulfide-releasing anti-inflammatory drugs, Trends Pharmacol Sci, 28, 501, 10.1016/j.tips.2007.09.003 Fiorucci, 2007, Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis, Br J Pharmacol, 150, 996, 10.1038/sj.bjp.0707193 Wallace, 2010, Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346), Br J Pharmacol, 159, 1236, 10.1111/j.1476-5381.2009.00611.x Sartor, 1997, Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases, Am J Gastroenterol, 92, 5S Stallmach, 1999, Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice, Gastroenterology, 117, 866, 10.1016/S0016-5085(99)70345-8 Ajuebor, 2001, The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat, J Immunol, 166, 552, 10.4049/jimmunol.166.1.552 Morris, 1989, Hapten-induced model of chronic inflammation and ulceration in the rat colon, Gastroenterology, 96, 795, 10.1016/0016-5085(89)90904-9 Fiorucci S, PB, Mencarelli A, Fanini C, Morelli A, Del Soldato P. NO-aspirin (NCX4016) modulates pro-inflammatory cytokines and COX isoenzymes. An human study. Abstract, 2002. Distrutti, 2006, 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity, J Pharmacol Exp Ther, 319, 447, 10.1124/jpet.106.106435 Thun, 2002, Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues, J Natl Cancer Inst, 94, 252, 10.1093/jnci/94.4.252 Kashfi, 2009, Anti-inflammatory agents as cancer therapeutics, Adv Pharmacol, 57, 31, 10.1016/S1054-3589(08)57002-5 Chattopadhyay, 2012, Hydrogen sulfide-releasing NSAIDs inhibit the growth of human cancer cells: a general property and evidence of a tissue type-independent effect, Biochem Pharmacol, 83, 715, 10.1016/j.bcp.2011.12.018 Chattopadhyay, 2012, Hydrogen sulfide-releasing aspirin suppresses NF-kappaB signaling in estrogen receptor negative breast cancer cells in vitro and in vivo, Biochem Pharmacol, 83, 723, 10.1016/j.bcp.2011.12.019 Biswas, 2001, The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for estrogen receptor negative breast cancers, Proc Natl Acad Sci USA, 98, 10386, 10.1073/pnas.151257998 Switzer, 2012, Dithiolethiones inhibit NF-kappaB activity via covalent modification in human estrogen receptor-negative breast cancer, Cancer Res, 72, 2394, 10.1158/0008-5472.CAN-11-3115 Chattopadhyay, 2012, Hydrogen sulfide-releasing aspirin modulates xenobiotic metabolizing enzymes in vitro and in vivo, Biochem Pharmacol, 83, 733, 10.1016/j.bcp.2011.12.020 Wallace, 2000, Nitric oxide in mucosal defense: a little goes a long way, Gastroenterology, 119, 512, 10.1053/gast.2000.9304 Kashfi, 2007, The mechanism of action of nitric oxide-donating aspirin, Biochem Biophys Res Commun, 358, 1096, 10.1016/j.bbrc.2007.05.038 Hulsman, 2007, Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin, J Med Chem, 50, 2424, 10.1021/jm061371e Dunlap, 2007, Quinone formation as a chemoprevention strategy for hybrid drugs: balancing cytotoxicity and cytoprotection, Chem Res Toxicol, 20, 1903, 10.1021/tx7002257 BioSpace. National Cancer Institute Ends Colon Cancer Trial with NicOx SA (NCOX.F)’s NCX 4016. http://wwwbiospacecom/news_storyaspx?StoryId=60278; 2007. Kashfi, 2005, Positional isomerism markedly affects the growth inhibition of colon cancer cells by nitric oxide-donating aspirin in vitro and in vivo, J Pharmacol Exp Ther, 312, 978, 10.1124/jpet.104.075994 Kodela, 2012, NOSH-Aspirin. A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals, ACS Med Chem Lett, 3, 257, 10.1021/ml300002m Chattopadhyay, 2012, NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model, Biochem Biophys Res Commun, 419, 523, 10.1016/j.bbrc.2012.02.051 Bilska, 2010, Effects of aspirin on the levels of hydrogen sulfide and sulfane sulfur in mouse tissues, Pharmacol Rep, 62, 304, 10.1016/S1734-1140(10)70270-X Wilinski, 2011, Paracetamol (acetaminophen) decreases hydrogen sulfide tissue concentration in brain but increases it in the heart, liver and kidney in mice, Folia Biol (Krakow), 59, 41, 10.3409/fb59_1-2.41-44 Wilinski, 2011, Atorvastatin affects the tissue concentration of hydrogen sulfide in mouse kidneys and other organs, Pharmacol Rep, 63, 184, 10.1016/S1734-1140(11)70414-5 Wojcicka, 2011, Differential effects of statins on endogenous H2S formation in perivascular adipose tissue, Pharmacol Res, 63, 68, 10.1016/j.phrs.2010.10.011 Salloum, 2009, Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide, Circulation, 120, S31, 10.1161/CIRCULATIONAHA.108.843979