Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits

Pharmacology and Therapeutics

Volumn 141, Issue 2, 2014, Pages 150-159

  Rushworth, Gordon F ^a   Megson, Ian L ^b  

^a Centre for Health Science   (United Kingdom)

^b UNIVERSITY OF THE HIGHLANDS AND ISLANDS   (United Kingdom)

Author keywords

Antioxidant; Glutathione; N acetylcysteine

Indexed keywords

ACETYLCYSTEINE; ANTIOXIDANT; GLUTATHIONE; PARACETAMOL;

BIOCHEMISTRY; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CLINICAL PHARMACOLOGY; CONTRAST INDUCED NEPHROPATHY; DIABETES MELLITUS; DRUG INTOXICATION; DRUG MECHANISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LUNG DISEASE; LUNG FIBROSIS; MENTAL DISEASE; METABOLISM; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW;

ACUTE KIDNEY INJURY; AKI; ANTIOXIDANT; BAL; BRONCHOALVEOLAR LAVAGE; CF; CHRONIC OBSTRUCTIVE PULMONARY DISEASE; CIN; CONTRAST-INDUCED NEPHROPATHY; COPD; CYSTIC FIBROSIS; GCL; GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; GLUTATHIONE DISULFIDE; GLUTATHIONE PEROXIDISES; GSH; GSH PX; GSSG; IDIOPATHIC PULMONARY FIBROSIS; INTRAVENOUS; IPF; IV; N-ACETYL-L-CYSTEINE; N-ACETYLCYSTEINE; N-ACEYTL-P-BENZOQUINONIMINE; NAC; NAPQI; REACTIVE OXYGEN SPECIES; ROS;

ACETYLCYSTEINE; ANIMALS; ANTIOXIDANTS; GLUTATHIONE; HUMANS; PRODRUGS;

EID: 84891883913     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2013.09.006     Document Type: Review

References (136)

1. J.C. Adair, J.E. Knoefel, and N. Morgan Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease Neurology 57 2001 1515 1517
2. M. Aitio N-acetylcysteine - passe-partout or much ado about nothing? Br J Clin Pharmacol 61 2006 5 15
3. A. Arrigo Gene expression and the thiol redox state Free Radic Biol Med 27 1999 936 944
4. O.I. Aruoma, B. Halliwell, B.M. Hoey, and J. Butler The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid Free Radic Biol Med 6 1989 593 597
5. E. Aslanger, B. Uslu, C. Akdeniz, N. Polat, Y. Cizgici, and H. Oflaz Intrarenal application of N-acetylcysteine for the prevention of contrast medium-induced nephropathy in primary angioplasty Coron Artery Dis 23 2012 265 270
6. C.S.R. Baker, A. Wragg, S. Kumar, R. De Palma, L.R.I. Baker, and C.J. Knight A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study J Am Coll Cardiol 41 2003 2114 2118
7. W.J. Banner, M. Koch, D.M. Capin, S.B. Hopf, S. Chang, and T.G. Tong Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds Toxicol Appl Pharmacol 83 1986 142 147
8. G.M. Bartoli, and H. Sies Reduced and oxidized glutathione efflux from liver FEBS Lett 86 1978 89 91
9. A. Becker, and K.F. Soliman The role of intracellular glutathione in inorganic mercury-induced toxicity in neuroblastoma cells Neurochem Res 34 2009 1677 1684
10. J. Behr, K. Maier, B. Degenkolb, F. Krombach, and C. Volgelmeier Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis: adjunctive therapy to maintenance immunosuppression Am J Respir Crit Care Med 156 1997 1897 1901
11. M. Berk, D.L. Copolov, O. Dean, K. Lu, S. Jeavons, and I. Schapkaitz et al. N-acetyl cysteine for depressive symptoms in bipolar disorder - a double-blind randomized placebo-controlled trial Biol Psychiatry 64 2008 468 475
12. M. Berk, D. Copolov, O. Dean, K. Lu, S. Jeavons, and I. Schapkaitz et al. N-acetyl cysteine as a glutathione precursor for schizophrenia - a double-blind, randomized, placebo-controlled trial Biol Psychiatry 64 2008 361 368
13. M. Berk, O. Dean, S.M. Cotton, C.S. Gama, F. Kapczinski, and B.S. Fernandes et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial J Affect Disord 135 2011 389 394
14. -/- mice Biochem Biophys Res Commun 338 2005 1368 1373
15. M. Blanusa, V.M. Varnai, M. Piasek, and K. Kostial Chelators as antidotes of metal toxicity: therapeutic and experimental aspects Curr Med Chem 12 2005 2771 2794
16. L. Borgstrom, B. Kagedal, and O. Paulsen Pharmacokinetics of N-acetylcysteine in man Eur J Clin Pharmacol 31 1986 217 222
17. R. Brandao, F.W. Santos, G. Zeni, J.B. Rocha, and C.W. Nogueira DMPS and N-acetylcysteine induce renal toxicity in mice exposed to mercury Biometals 19 2006 389 398
18. H. Buyukhatipoglu, Y. Sezen, A. Yildiz, M. Bas, I. Kirhan, and T. Ulas et al. N-acetylcysteine fails to prevent renal dysfunction and oxidative stress after noniodine contrast media administration during percutaneous coronary interventions Pol Arch Med Wewn 120 2010 383 389
19. A.M. Cantin, R.C. Hubbard, and R.G. Crystal Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis Am Rev Respir Dis 139 1989 370 372
20. A.M. Cantin, S.L. North, G.A. Fells, R.C. Hubbard, and R.G. Crystal Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis J Clin Invest 79 1987 1665 1673
21. N. Carbonell, R. Sanjuan, M. Blasco, A. Jorda, and A. Miguel N-acetylcysteine: short-term clinical benefits after coronary angiography in high-risk renal patients Rev Esp Cardiol 63 2010 12 19
22. P.A. Chyka, A.Y. Butler, B.J. Holliman, and M.I. Herman Utility of acetylcysteine in treating poisonings and adverse drug reactions Drug Saf 22 2000 123 148
23. I.A. Cotgreave, M. Berggren, T.W. Jones, J. Dawson, and P. Moldeus Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems Biopharm Drug Dispos 8 1987 337 386
24. I.A. Cotgreave, A. Eklund, K. Larsson, and P.W. Moldeus No penetration of orally administered N-aceylcysteine into bronchoalveolar lavage fluid Eur J Respir Dis 70 1987 73 77
25. I. Cotgreave, P. Moldéus, and I. Schuppe The metabolism of N-acetylcysteine by human endothelial cells Biochem Pharmacol 42 1991 13 16
26. R.C. Dart, A.R. Erdman, K.R. Olson, G. Christianson, A.S. Manoguerra, and P.A. Chyka et al. Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management Clin Toxicol 44 2006 1 18
27. N. Dauletbaev, P. Fisher, B. Aulbach, J. Gross, W. Kusche, and U. Thyroff-Friesinger et al. A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis Eur J Med Res 14 2009 352 358
28. N. Dauletbaev, K. Viel, R. Buhl, T.O.F. Wagner, and J. Bargon Glutathione and glutathione peroxidase in sputum samples of adult patients with cystic fibrosis J Cyst Fibros 3 2004 119 124
29. S. De Flora, C. Benicelli, A. Camoirano, D. Serra, M. Romano, and G.A. Rossi et al. In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds Carcinogenesis 6 1985 1735 1745
30. S. De Flora, C. Bennicelli, P. Zanacchi, A. Camoirano, A. Morelli, and A. De Flora In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens Carcinogenesis 5 1984 505 510
31. S. De Flora, A. Izzotti, F. D'Agostini, and R.M. Balansky Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points Carcinogenesis 22 2001 999 1013
32. S.C. De Rosa, M.D. Zaretsky, J.G. Dubs, M. Roederer, M. Anderson, and A. Green et al. N-acetylcysteine replenishes glutathione in HIV infection Eur J Clin Invest 30 2000 915 929
33. O. Dean, F. Giorlando, and M. Berk N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action J Psychiatry Neurosci 36 2011 78 86
34. M. Demedts, J. Behr, R. Buhl, U. Costabel, R. Dekhuijzen, and H.M. Jansen High-dose acetylcysteine in idiopathic pulmonary fibrosis N Engl J Med 353 2005 2229 2242
35. D.A. Dickinson, A. Levonen, D.R. Moellering, E.K. Arnold, H. Zhang, and V.M. Darley-Usmar et al. Human glutamate cysteine ligase gene regulation through the electrophile response element Free Radical Biol Med 37 2004 1152 1159
36. L.F. Drager, L. Andrade, J.F.B. de Toledo, F.R.M. Laurindo, L.A.M. Cesar, and A.C. Seguro Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury Nephrol Dial Transplant 19 2004 1803 1807
37. R. Dworski Oxidant stress in asthma Thorax 55 2000 S51 S53
38. D. Fioret, R.L. Perez, and J. Roman Management of idiopathic pulmonary fibrosis Am J Med Sci 341 2011 450 453
39. R.J. Flanagan, and T.J. Meredith Use of N-acetylcysteine in clinical toxicology Am J Med 91 1991 S131 S139
40. L. Gao, K.J. Kim, J.R. Yankaskas, and H.J. Forman Abnormal glutathione transport in cystic fibrosis airway epithelia Am J Physiol Lung Cell Mol Physiol 277 1999 L113 L118
41. K.R. Gibson, I.L. Neilson, F. Barrett, T.J. Winterburn, S. Sharma, and S.M. Macrury et al. Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity J Cardiovasc Pharmacol 54 2009 319 326
42. K.R. Gibson, T.J. Winterburn, F. Barrett, S. Sharma, S. MacRury, and I.L. Megson Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes Cardiovasc Diabetol 10 2011 1 8
43. D. Giustarini, A. Milzani, I. Dalle-Donne, D. Tsikas, and R. Rossi N-acetylcysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential Biochem Pharmacol 84 2012 1522 1533
44. I. Goldenberg, M. Shechter, S. Matetzky, M. Jonas, M. Adam, and H. Pres et al. Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography: a randomized controlled trial and review of the current literature Eur Heart J 25 2004 212 218
45. S. Gosselin, R.S. Hoffman, D.N. Juurlink, I. Whyte, M. Yarema, and J. Caro Treating acetaminophen overdose: thresholds, costs and uncertainties Clin Toxicol 51 2013 252 378
46. T. Gray, R.S. Hoffman, and D.N. Bateman Intravenous paracetamol - an international perspective of toxicity Clin Toxicol 49 2011 150 152
47. K.M. Gray, N.L. Watson, M.J. Carpenter, and S.D. LaRowe N-acetylcysteine (NAC) in young marijuana users: An open-label pilot study Am J Addict 19 2010 187 189
48. J.L. Green, K.J. Heard, K.M. Reynolds, and D. Albert Oral and intravenous acetylcysteine for treatment of acetaminophen toxicity: a systematic review and meta-analysis West J Emerg Med 14 2013 218 226
49. K.K. Griendling, and R.W. Alexander Oxidative stress and cardiovascular disease Circulation 96 1997 3264 3275
50. O.W. Griffith Biologic and pharmacologic regulation of mammalian glutathione synthesis Free Radic Biol Med 27 1999 922 935
51. H.S. Gurm, D.E. Smith, O. Berwanger, D. Share, T. Schreiber, and M. Moscucci et al. Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention JACC Cardiovasc Interv 5 2012 98 104
52. B. Halliwell Vitamin C: Antioxidant or pro-oxidant in vivo Free Radic Res 25 1996 439 454
53. A.D. Halpner, G.J. Handelman, J.M. Harris, C.A. Belmont, and J.B. Blumberg Protection by vitamin C of loss of vitamin E in cultured rat hepatocytes Arch Biochem Biophys 359 1998 305 309
54. A.Y. Hardan, L.K. Fung, R.A. Libove, T.V. Obukhanych, S. Nair, and L.A. Herzenberg et al. A randomised controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 71 2012 956 961
55. P.M. Harrison, R. Keays, G.P. Bray, G.J.M. Alexander, and R. Williams Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine Lancet 335 1990 1572 1573
56. M. Hayakawa, H. Miyashita, I. Sakamoto, M. Kitagawa, H. Tanaka, and Hideyo Y. et al. Evidence that reactive oxygen species do not mediate NF-kB activation EMBO J 22 2003 3356 3366
57. L.A. Herzenberg, S.C. De Rosa, J.G. Dubs, M. Roederer, M.T. Anderson, and S.W. Ela et al. Glutathione deficiency is associated with impaired survival in HIV disease Proc Natl Acad Sci U S A 94 1997 1967 1972
58. M.R. Holdiness Clinical pharmacokinetics of N-acetylcysteine Clin Pharmacokinet 20 1991 123 134
59. T. Hsu, M. Huang, S. Yu, D.H. Yen, W. Kao, and Y. Chen et al. N-acetylcysteine for the prevention of contrast-induced nephropathy in the emergency department Intern Med 51 2012 2709 2714
60. G.A. Hurst, P.B. Shaw, and C.A. LeMaistre Laboratory and clinical evaluation of the mucolytic properties of acetylcysteine Am Rev Respir Dis 96 1967 962 970
61. S. Jo N-acetylcysteine for prevention of contrast-induced nephropathy: a narrative review Korean Circ J 41 2011 695 702
62. W.M. Johnson, A.L. Wilson-Delfosse, and J.J. Mieyal Dysregulation of glutathione homeostasis in neurodegenerative diseases Nutrients 4 2012 1399 1440
63. D. Joshi, D.K. Mittal, S. Shrivastava, and S. Shukla Protective role of thiol chelators against dimethylmercury induced toxicity in male rats Bull Environ Contam Toxicol 84 2010 613 617
64. M.Z. Kanter Comparison of oral and iv acetylcysteine in the treatment of acetaminophen poisoning Am J Health Syst Pharm 63 2006 1821 1827
65. P. Kaur, M. Aschner, and T. Syversen Glutathione modulation influences methyl mercury induced neurotoxicity in primary cell cultures of neurones and astrocytes Neurotoxicology 27 2006 492 500
66. P. Kirkham, and I. Rahman Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy Pharmacol Ther 111 2006 476 494
67. L.A. Knackstedt, S. LaRowe, P. Mardikian, R. Malcolm, H. Upadhyaya, and S. Hedden et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans Biol Psychiatry 65 2009 841 845
68. F. Koc, K. Ozdemir, M.G. Kaya, O. Dogdu, M.A. Vatankulu, and S. Ayhan et al. Intravenous N-acetylcysteine plus high-dose hydration versus high-dose hydration and standard hydration for the prevention of contrast-induced nephropathy: CASIS - A multicenter prospective controlled trial Int J Cardiol 155 2012 418 423
69. D.L. Lafleur, C. Pittenger, B. Kelmendi, T. Gardner, S. Wasylink, and R.T. Malison et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder Psychopharmacology 184 2006 254 256
70. D. Lapenna, S. de Gioia, G. Ciofani, A. Mezzetti, S. Ucchino, and A.M. Calafiore et al. Glutathione-related antioxidant defenses in human atherosclerotic plaques Circulation 97 1998 1930 1934
71. S. Lavoie, M.M. Murray, P. Deppen, M.G. Knyazeva, M. Berk, and O. Boulat et al. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients Neuropsychopharmacology 33 2008 2187 2199
72. M. Le Brocq, S.J. Leslie, P. Milliken, and I.L. Megson Endothelial dysfunction: From molecular mechanisms to measurement, clinical implications, and therapeutic opportunities Antioxid Redox Signal 10 2008 1631 1674
73. D. Leelarungrayub, R. Khansuwan, P. Pothongsunun, and J. Klaphajone N-acetylcysteine supplementation controls total antioxidant capacity, creatinine kinase, lactate, and tumour necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men Oxid Med Cell Longev 2011 2011 329643
74. X. Li, Z.C. Qu, and J.M. May GSH is required to recycle ascorbic acid in cultured liver cell lines Antioxid Redox Signal 3 2001 1089 1097
75. 2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation Free Radic Biol Med 25 1998 287 297
76. H.K. Lota, and A.U. Wells The evolving pharmacotherapy of pulmonary fibrosis Expert Opin Pharmacother 14 2013 79 89
77. E.S. Louwerse, G.J. Weverling, P.M. Bossuyt, F.E. Meyje, and J.M. de Jong Randomized double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis Arch Neurol 52 1995 559 564
78. S.C. Lu Regulation of glutathione synthesis Mol Aspects Med 30 2009 42 59
79. M.E. Lund, W.J. Banner, T.W. Clarkson, and M. Berlin Treatment of acute methylmercury ingestion by hemodialysis with N-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate J Toxicol Clin Toxicol 22 1984 31 49
80. J. Luo, T. Tsuji, H. Yasuda, Y. Sun, Y. Fujigaki, and A. Hishida The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats Nephrol Dial Transplant 23 2008 2198 2205
81. T.M. Maher Current and future therapies for idiopathic pulmonary fibrosis Clin Pulm Med 18 2011 257 264
82. P.N. Mardikian, S.D. LaRowe, S. Hedden, P.W. Kalivas, and R.J. Malcolm An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study Prog Neuropsychopharmacol Biol Psychiatry 31 2007 389 394
83. M. Marmor, P. Alcabes, S. Titus, K. Frenkel, K. Krasinski, and A. Penn et al. Low serum thiol levels predict shorter times-to-death among HIV-infected injecting drug users AIDS 11 1997 1389 1393
84. V. Martina, A. Masha, V.R. Gigliardi, L. Brocato, E. Manzato, and A. Berchio et al. Long-term N-acetylcysteine and l-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes Diabetes Care 31 2008 940 944
85. J.M. May, Z.C. Qu, and S. Mendiratta Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid Arch Biochem Biophys 349 1998 281 289
86. L. Mazzanti, and B. Mutus Diabetes-induced alterations in platelet metabolism Clin Biochem 30 1997 509 515
87. R.J. McDonald, J.S. McDonald, J.P. Bida, R.E. Carter, C.J. Fleming, and S. Misra et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology 267 2013 106 118
88. R.A. McPherson, and G. Hardy Cysteine: the Fun-Ke nutraceutical Nutrition 28 2012 336 337
89. A. Meister, and M.E. Anderson Glutathione Annu Rev Biochem 52 1983 711 760
90. A. Meyer, R. Buhl, S. Kampf, and H. Magnussen Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals Am J Respir Crit Care Med 152 1995 1055 1060
91. A. Meyer, R. Buhl, and H. Magnussen The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis Eur Respir J 7 1994 431 436
92. V. Montecinos, P. Guzmán, V. Barra, M. Villagrán, C. Muñoz-Montesino, and K. Sotomayor et al. Vitamin C is an essential antioxidant that enhances survival of oxidatively stressed human vascular endothelial cells in the presence of a vast molar excess of glutathione J Biol Chem 282 2007 15506 15515
93. Multicentre Study Group Long-term oral acetylcysteine in chronic bronchitis. A double-blind controlled study Eur J Respir Dis 61 1980 93 108
94. N.J. Nambiar Management of paracetamol poisoning: The old and the new J Clin Diagn Res 6 2012 1101 1104
95. A.G. Nicholson, T.V. Colby, R.M. du Bois, D.M. Hansell, and A.U. Wells The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis Am J Respir Crit Care Med 162 2000 2213 2217
96. B. Olsson, M. Johansson, J. Gabrielsson, and P. Bolme Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine Eur J Clin Pharmacol 34 1988 77 82
97. N. Pakravan, W.S. Waring, S. Sharma, C. Ludlam, I.L. Megson, and N. Bateman Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose Clin Toxicol 46 2008 697 702
98. P. Parfrey The clinical epidemiology of contrast-induced nephropathy Cardiovasc Intervent Radiol 28 Suppl. 2 2005 S3 S11
99. L. Pendyala, and P.J. Creaven Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial Cancer Epidemiol Biomarkers Prev 4 1995 245 251
100. G.M. Pieper, and W. Siebeneich Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction J Cardiovasc Pharmacol 32 1998 101 105
101. A. Pompella, A. Visvikis, A. Paolicchi, V. De Tata, and A.F. Casini The changing faces of glutathione, a cellular protagonist Biochem Pharmacol 66 2003 1499 1503
102. P.J. Poole, and P.N. Black Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: Systematic review Br Med J 332 2001 1 6
103. L.F. Prescott, R.N. Illingworth, J.A. Critchley, M.J. Stewart, R.D. Adam, and A.T. Proudfoot Intravenous N-acetylcysteine: The treatment of choice for paracetamol poisoning Br Med J 2 1979 1097 1100
104. L.F. Prescott, J. Park, A. Ballantyne, P. Adriaenssens, and A.T. Proudfoot Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine Br Med J 2 1977 432 434
105. L.F. Prescott, G.R. Sutherland, J. Park, I.J. Smith, and A.T. Proudfoot Cysteamine, methionine, and penicillamine in the treatment of paracetamol poisoning Lancet 308 1976 109 113
106. G. Raghu, K.J. Anstrom, T.E. King, J.A. Lasky, F.J. Martinez, and A. Arbor Prednisolone, azathioprine, and N-acetylcysteine for pulmonary fibrosis N Engl J Med 366 2012 1968 1977
107. I. Rahman, and W. MacNee Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches Free Radic Biol Med 28 2000 1405 1420
108. F. Ratjen, and H. Grasemann New therapies in cystic fibrosis Curr Pharm Des 18 2012 614 627
109. M.G. Riga, L. Chelis, S. Kakolyris, S. Papadopoulos, S. Stathakidou, and E. Chamalidou et al. Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: A feasible method with promising efficacy Am J Clin Oncol 36 2013 1 6
110. M. Rosenblat, and M. Aviram Macrophage glutathione content and glutathione peroxidase activity are inversely related to cell-mediated oxidation of LDL: in vitro and in vivo studies Free Radic Biol Med 24 1998 305 317
111. S.M. Rowe, and J.P. Clancy Advances in cystic fibrosis therapies Curr Opin Pediatr 18 2006 604 613
112. R.M. Rudd, R.J. Prescott, J.C. Chalmers, and I.D.A. Johnston British Thoracic Society Study on cryptogenic fibrosing alveolitis: response to treatment and survival Thorax 62 2007 62 66
113. R. Ryan British National Formulary 2012 BMA, RPS
114. C. Saito, C. Zwingmann, and H. Jaechke Novel mechanisms of protection against hepatotoxicity in mice by glutathione and N-acetylcysteine Hepatology 51 2010 246 254
115. Y. Samuni, S. Goldstein, O.M. Dean, and M. Berk The chemistry and biological activities of N-acetylcysteine Biochim Biophys Acta 1830 2013 4117 4129
116. E.A. Sandilands, and D.N. Bateman Adverse reactions associated with acetylcysteine Clin Toxicol 47 2009 81 88
117. E.A. Sandilands, S. Camerson, F. Parterson, S. Donaldson, L. Briody, and J. Crowe et al. Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol BMC Clin Pharmacol 12 2012 1 8
118. S.J. Shalansky, G.E. Pate, A. Levin, and J.G. Webb N-acetylcysteine for prevention of radiocontrast induced nephrotoxicity: The importance of dose and route of administration Heart 91 2005 997 999
119. A.L. Sheffner, E.M. Medler, L.W. Jacobs, and H.P. Sarett The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine Am Rev Respir Dis 90 1964 721 729
120. V. Sosa, T. Moliné, R. Somoza, R. Paciucci, H. Kondoh, and M.E. Leonart Oxidative stress and cancer: an overview Ageing Res Rev 12 2013 376 390
121. K. Stadler Oxidative stress in diabetes Adv Exp Med Biol 771 2012 272 287
122. C. Stey, J. Steurer, S. Bachmann, T.C. Medici, and M.R. Tramer The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review Eur Respir J 16 2000 253 262
123. J.S. Suk, N.J. Boylan, K. Trehan, B.C. Tang, C.S. Schneider, and J.G. Lin et al. N-acetylcysteine enhances cystic fibrosis sputum penetration an airway gene transfer by highly compacted DNA nanoparticles Mol Ther 19 2011 1981 1989
124. Z. Sun, Q. Fu, L. Cao, W. Jin, L. Cheng, and Z. Li Intravenous N-acetylcysteine for prevention of contrast-induced nephropathy: a meta-analysis of randomised, controlled trials PLoS One 8 2013 1 8
125. K. Suzuki Anti-oxidants for therapeutic use: Why are only a few drugs in clinical use? Adv Drug Deliv Rev 61 2009 287 289
126. A.B. Tattersall, K.M. Bridgman, and A. Huitson Acetylcysteine (Fabrol) in chronic bronchitis - a study on general practice J Int Med Res 11 1983 279 284
127. R. Tirouvanziam, C.K. Conrad, T. Bottiglieri, L.A. Herzenberg, R.B. Moss, and L.A. Herzenberg High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis Proc Natl Acad Sci U S A 103 2006 4628 4633
128. A.T. Treweeke, T.J. Winterburn, I. MacKenzie, F. Barrett, C. Barr, and G.F. Rushworth et al. N-acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial Diabetologia 55 2012 2920 2928
129. L. Turell, R. Radi, and B. Alvarez The thiol pool in human plasma: the central contribition of albumin to redox processes Free Radic Biol Med 65 2013 244 253
130. M.E. Ullian, A.K. Gelasco, W.R. Fitzgibbon, C.N. Beck, and T.A. Morinelli N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth muscle cells J Am Soc Nephrol 16 2005 2346 2353
131. N. van Zandwijk, O. Dalesio, U. Pastorino, N. de Vries, and H. van Tinteren EUROSCAN, a randomised trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer J Natl Cancer Inst 92 2000 977 986
132. W.S. Waring Criteria for acetylcysteine treatment and clinical outcomes after paracetamol poisoning Expert Rev Clin Pharmacol 5 2012 311 318
133. W.S. Waring, A.F. Stephen, O.D. Robinson, M.A. Dow, and J.M. Pettie Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose Clin Toxicol 46 2008 496 500
134. C.C. Winterbourne, and D. Metodiewa Reactivity pf biologically important thiol compounds with superoxide and hydrogen peroxide Free Radic Biol Med 27 1999 322 328
135. R.K. Zalups, and S. Ahmad Transport of N-acetylcysteine s-conjugates of methylmercury in Madin-Darby canine kidney cells stably transfected with human isoform of organic anion transporter 1 J Pharmacol Exp Ther 314 2005 1158 1168
136. R.K. Zalups, and D.W. Barfuss Participation of mercuric conjugates of cysteine, homocysteine, and N-acetylcysteine in mechanisms involved in the renal tubular uptake of inorganic mercury J Am Soc Nephrol 9 1998 551 561