The Overlooked Compound That Saves LivesMay 2010
By Julius Goepp, MD
Lung Disease Defense
Chronic obstructive pulmonary disease (COPD), which includes chronic bronchitis and chronic emphysema, is a rapidly growing problem with global impact.35 COPD is the result of years of oxidative damage to delicate lung tissue, with resultant chronic inflammatory changes.36 The disease is worsened by air pollution and cigarette smoking, but is by no means limited to people with those exposures. Over time, victims’ damaged airways may become colonized with dangerous bacteria, leading to chronic infection and still more inflammation in a vicious cycle. Current treatment consists mainly of anti-inflammatory steroids and lung-opening medications used in asthma, with the addition of antibiotics when infection threatens.
With its ability to reduce oxidative stress and simultaneously quash chronic inflammatory changes, NAC is emerging as a game-changing therapy in COPD. A randomized pilot study of adults with acute exacerbation of chronic bronchitis and positive bacterial culture in the sputum demonstrated that 600 mg of NAC twice daily led to a near doubling of the rate of bacterial eradication compared with standard therapy, while reducing the number and duration of acute exacerbations and improving quality of life.35 NAC treatment of patients with moderate-to-severe COPD improved their physical performance on lung function tests, especially after exercise.37
Patients with advanced COPD frequently require low-dose oxygen therapy because of their lung damage. In many cases, however, oxidative stress induced by the disease has already rendered them glutathione deficient, so they have diminished protection against ongoing oxidation.38 NAC administration at doses of 1,200-1,800 mg/day along with low-dose oxygen powerfully counteracts this oxidative stress. At doses of 1,800 mg per day, it has been shown to completely prevent further protein oxidation.38 A dose of 600 mg twice daily over a 2-month period rapidly reduced exhaled hydrogen peroxide, a measure of oxidative burden in COPD sufferers.39
In one study utilizing a dose of just 600 mg per day for 10 weeks, NAC disrupted the molecular relationship between oxidative stress and inflammation, protecting lung tissue.36 When NAC is added to inhaled corticosteroids, still further reductions in inflammatory parameters are found.40
Emphysema can be the unfortunate endpoint of advanced COPD, with lung tissue breaking down and losing much of its ability to exchange oxygen and carbon dioxide. Animal studies show that NAC attenuates COPD-related lung damage and emphysema by supporting expression of important protective genes in the cells lining the lung.41
Another devastating chronic lung condition called idiopathic pulmonary fibrosis (IPF) also involves increased oxidative burden and a deficiency of glutathione in lung tissue and fluids.42 This progressive disease has a poor prognosis, even when treated with standard corticosteroids and powerful prescription anti-inflammatory drugs.43,44 The median survival is only about 3 years regardless of therapy.45
Oral NAC supplements now offer a ray of hope for IPF sufferers. NAC significantly increases lung glutathione levels in both animal and human studies of IPF.42,46 Given as an aerosol treatment, NAC may delay disease progression, and at doses of 600 mg three times daily preserves lung vital capacity and gas exchange better than standard therapy alone.43,44
In summary, evidence suggests that NAC may offer benefits at doses of 600 mg 2-3 times daily for people who have, or are at risk for, chronic lung conditions such as COPD and IPF (idiopathic pulmonary fibrosis).
Reduce Exercise-Induced Oxidative Stress
Health-conscious people know that regular moderate exercise is vital to maintaining the integrity of the human body. Of course, everything has its price, and the rapid increase in metabolic activity during exercise produces some unwanted side effects.20 These include an increase in oxidative stress that can overwhelm the body’s antioxidant defense mechanisms and lead to tissue damage and abnormal activity of certain immune system cells.47,48 Exercise also increases plasma levels of inflammatory cytokines such as TNF-alpha and various interleukins.49 The solution, of course, is not to reduce your exercise regimen, but rather to look for ways to optimize the way your body handles those metabolic challenges.
NAC, with its powerful antioxidant and gene-regulating powers, is an excellent means of maintaining good exercise performance and limiting the damage caused by oxidative stress in the process. Supplementation with NAC (2,000 mg daily for 3 days, followed by 800 mg prior to exercise) in strenuously exercising adults lowered key interleukin levels to undetectable amounts and abolished the exercise-induced TNF-alpha response.49 And in patients with severe COPD, NAC supplementation improved exercise endurance time by 25% compared with placebo, while significantly reducing levels of oxidative molecules released by stimulated immune cells.50 NAC supplementation also dramatically curtailed production of oxidized proteins in this group of highly oxidant-stressed chronically ill patients.
In vigorously exercising men, 1,800 mg per day of NAC prevented the expected decline in intracellular antioxidant levels and increased activity of the enzyme responsible for recycling and restoring glutathione to normal levels, protecting cells from oxidative stress.51 And in mice, NAC supplementation significantly protected brain tissue against exercise-induced oxidative changes.52 NAC also preserves normal levels of vital lymphocytes, which can decline after vigorous exercise.48,53-55
Regular supplementation with NAC at up to 1,800-2,000 mg per day may be an effective means of optimizing exercise performance while minimizing the effects of exercise-induced metabolic stress.
Bring Glucose Levels Under Control
Oxidative stress and inflammation are closely linked to insulin resistance and rising blood glucose levels. These effects are not limited to those with diabetes, but in fact are found even in obese, non-diabetic people and those with metabolic syndrome.56 There are multiple steps in the cascade of events leading from oxidation to damaged insulin receptors and insulin resistance, so it makes sense to seek a supplement that can target many of those steps independently.57,58 NAC is emerging as one such multi-targeted supplement.56
Over time, chronic high blood sugar initiates a downward spiral by helping generate advanced glycation end-products (AGEs) that then impair normal responses to insulin, perpetuating elevated sugar levels. NAC reverses those effects in laboratory models.22 Increasing blood sugar levels in laboratory animals triggers a pro-inflammatory response in fat tissue—also effectively reduced by NAC.21 In an experiment that recreates a common human dietary trend, rats were given a diet high in the sweetener fructose, which produced increased blood pressure, plasma insulin levels, and triglyceride levels. Yet all of these dangerous physiological alterations were inhibited by NAC.59
Human studies of NAC to improve insulin sensitivity have recently appeared, especially in a group of people typically very difficult to treat. Profound insulin resistance is seen in women with polycystic ovary syndrome (PCOS), along with a variety of other metabolic disturbances. One study showed that NAC at 1,200 mg per day along with 1,600 mg of the amino acid arginine promoted a trend toward normal ovulatory cycles and substantially improved insulin sensitivity.60 A short-term study showed that 1,800 mg of NAC daily helped improve insulin sensitivity in women with PCOS.61
Virtually all Americans consume too many calories and are at risk for at least some degree of insulin resistance. Daily supplementation with NAC at 1,200 to 1,800 mg per day may help to reduce the impact and slow the damage wrought by AGEs.
The strong and growing links between oxidative stress, inflammation, and cancer make NAC a natural go-to compound for cancer chemoprevention. True to form, NAC has multiple anti-cancer activities acting at multiple targets to provide layers of cancer protection against a large variety of cancer types. NAC induces programmed cell death (apoptosis) in multiple types of human cancer cells.62 In human gastric cancer cells, NAC not only induces apoptosis, but also stops DNA synthesis, preventing cancer the cells from replicating.63 In melanoma cells, NAC inhibits NF-kB, preventing expression of signaling molecules needed by the cancer for growth.64 NAC inactivates and promotes destruction of c-Src, a chemical control molecule that is overproduced in many human cancers, providing a completely unique means of slowing or stopping tumor development.65 Finally, NAC protects DNA from breakage induced by ionizing radiation, but does not prevent cell destruction by radiation.66 That’s a vital finding because it means that NAC might allow radiation therapy to effectively kill cancer cells while minimizing the risk of so-called secondary cancers that could otherwise arise as side effects of the radiation.
Animal studies strengthen the case for NAC still further. NAC protects mice from cigarette smoke-induced lung cancers and other lung changes, a finding with enormous implications not only for current smokers but for ex-smokers and people exposed to second-hand smoke.67 NAC protects rats from chemically-induced liver cancers immediately following tumor initiation.68 This early interference with cancer development bodes well for NAC as a chemopreventive agent in the many human toxin-related cancers.
Human studies are similarly encouraging, even in the most challenging patient groups such as smokers. A randomized, double-blind chemoprevention trial of NAC 600 mg twice daily for 6 months vs. placebo in otherwise healthy smokers showed a significant reduction in formation of damaged or oxidized DNA segments, telltale early markers of cancer development in lung fluid.69 The same study also demonstrated reductions in abnormal, pre-cancerous cell changes in the mouths of supplemented smokers. These effects support the scientists’ conclusion that NAC can reduce tobacco smoke carcinogenicity in humans.
Colon cancer is another malignancy with strong links to oxidative stress and inflammation. Preliminary studies in humans show a 40% reduction in colorectal polyps in patients given 600 mg per day of NAC, compared with controls.70 In a group of people with a previous history of pre-cancerous colonic polyps, 800 mg per day of NAC for 12 weeks significantly reduced the proliferative index, indicating a decreased risk of colon cancer.71
Supplementing with 600-1,200 mg per day of NAC appears to be an entirely appropriate means of adding to your general cancer-prevention strategy.
Gastritis, Ulcers, Cancer, and Helicobacter pylori
Helicobacter pylori is a bacterium that colonizes various regions of the stomach and upper part of the small intestine. H. pylori infection produces major oxidative stress on tissues already vulnerable to extremes of pH and other chemical challenges, and the resulting inflammation produces pain and promotes development of gastric and esophageal cancers.19 NAC is an obvious candidate for fighting H. pylori infections, both because of its powerful ability to interfere with the oxidant-inflammation connection, and also because of its potential to break down some of the gastric mucous layer beneath which the organism hides.72
NAC fights H. pylori in at least two ways. It markedly inhibits growth of H. pylori both in culture dishes and in live mice, helping to reduce the total load of organisms present.72 But NAC also powerfully regulates gene expression in stomach lining cells, reducing hydrogen peroxide production induced by H. pylori, and decreasing activation of NF-kB and subsequent release of inflammatory cytokines.19,73 In human trials NAC improves eradication rates of H. pylori produced by standard treatment with antacids and antibiotics, when given at doses of 1,200 mg per day.74,75
People who have gastritis or gastroesophageal reflux disease (GERD) may be infected with H. pylori and may benefit from supplementation with 1,200 mg per day of NAC, especially during co-treatment with drugs to eradicate the organism.
N-acetyl cysteine is a broad-spectrum compound traditionally under-utilized in conventional medicine. A burst of new clinical research reveals that NAC exerts dual effects, functioning both as a powerful antioxidant that replenishes cellular antioxidant systems (glutathione in particular) and also as a potent modulator of gene expression, regulating inflammation at multiple, fundamental levels. It has been shown to be an effective intervention against influenza, chronic lung diseases, cancers, insulin resistance, and gastritis caused by H. pylori. NAC’s further value is shown in its ability to mitigate otherwise inevitable metabolic and immunological disturbances caused by exercise.
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1.Chun LJ, Tong MJ, Busuttil RW, Hiatt JR. Acetaminophen hepatotoxicity and acute liver failure. Clin Gastroenterol. 2009 Apr;43(4):342-9.
2.Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66.
3.Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 2009 Sep;60(3):3-21
4.Henke MO, Ratjen F. Mucolytics in cystic fibrosis. Paediatr Respir Rev. 2007 Mar;8(1):24-9.
5.Rogers DF. Mucoactive agents for airway mucus hypersecretory diseases. Respir Care. 2007 Sep;52(9):1176-93; discussion 93-7.
6.Marchetti A, Rossiter R. Managing acute acetaminophen poisoning with oral versus intravenous N-acetyl cysteine: a provider-perspective cost analysis. J Med Econ. 2009;12(4):384-91.
7.Saito C, Zwingmann C, Jaeschke H. Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetyl cysteine. Hepatology. Jan;51(1):246-54.
8.Chun LJ, Tong MJ, Busuttil RW, Hiatt JR. Acetaminophen hepatotoxicity and acute liver failure. J Clin Gastroenterol. 2009 Apr;43(4):342-9.
9.Atkuri KR, Mantovani JJ, Herzenberg LA. N-Acetyl cysteine—a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug;7(4):355-9.
10.Blesa S, Cortijo J, Mata M, et al. Oral N-acetyl cysteine attenuates the rat pulmonary inflammatory response to antigen. Eur Respir J. 2003 Mar;21(3):394-400.
11.Majano PL, Medina J, Zubia I, et al. N-Acetyl-cysteine modulates inducible nitric oxide synthase gene expression in human hepatocytes. J Hepatol. 2004 Apr;40(4):632-7.
12.Siddiqui A, Ancha H, Tedesco D, Lightfoot S, Stewart CA, Harty RF. Antioxidant therapy with N-acetyl cysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis. Dig Dis Sci. 2006 Apr;51(4):698-705.
13.Geiler J, Michaelis M, Naczk P, et al. N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol. Feb 1;79(3):413-20.
14.Jiang XF, Zeng WY, Pu J, Liu YM. Effect of N-acetyl cysteine on lipopolysaccharide stimulating IL-8 expression of human uterine smooth cell. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008 Mar;39(2):235-8.
15.Kim H, Seo JY, Roh KH, Lim JW, Kim KH. Suppression of NF-kappaB activation and cytokine production by N-acetyl cysteine in pancreatic acinar cells. Free Radic Biol Med. 2000 Oct 1;29(7):674-83.
16.Chen G, Shi J, Hu Z, Hang C. Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetyl cysteine. Mediators Inflamm. 2008;2008:716458.
17.Origuchi T, Migita K, Nakashima T, et al. Regulation of cyclooxygenase-2 expression in human osteoblastic cells by N-acetyl cysteine. J Lab Clin Med. 2000 Nov;136(5):390-4.
18.De Flora S, Izzotti A, D’Agostini F, Balansky RM. Mechanisms of N-acetyl cysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis. 2001 Jul;22(7):999-1013.
19.Seo JY, Kim H, Kim KH. Transcriptional regulation by thiol compounds in Helicobacter pylori-induced interleukin-8 production in human gastric epithelial cells. Ann N Y Acad Sci. 2002 Nov;973:541-5.
20.Kerksick C, Willoughby D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr. 2005;2:38-44.
21.Lin Y, Berg AH, Iyengar P, et al. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem. 2005 Feb 11;280(6):4617-26.
22.Unoki H, Bujo H, Yamagishi S, Takeuchi M, Imaizumi T, Saito Y. Advanced glycation end products attenuate cellular insulin sensitivity by increasing the generation of intracellular reactive oxygen species in adipocytes. Diabetes Res Clin Pract. 2007 May;76(2):236-44.
23.Dauletbaev N, Fischer P, Aulbach B, et al. A phase II study on safety and efficacy of high-dose N-acetyl cysteine in patients with cystic fibrosis. Eur J Med Res. 2009 Aug 12;14(8):352-8.
24.Us D. Cytokine storm in avian influenza. Mikrobiyol Bul. 2008 Apr;42(2):365-80.
25.De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetyl cysteine treatment. Eur Respir J. 1997 Jul;10(7):1535-41.
26.Knobil K, Choi AM, Weigand GW, Jacoby DB. Role of oxidants in influenza virus-induced gene expression. Am J Physiol. 1998 Jan;274(1 Pt 1):L134-42.
27.Kujime K, Hashimoto S, Gon Y, Shimizu K, Horie T. p38 mitogen-activated protein kinase and c-jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol. 2000 Mar 15;164(6):3222-8.
28.Lowy RJ, Dimitrov DS. Characterization of influenza virus-induced death of J774.1 macrophages. Exp Cell Res. 1997 Aug 1;234(2):249-58.
29.Ungheri D, Pisani C, Sanson G, et al. Protective effect of n-acetyl cysteine in a model of influenza infection in mice. Int J Immunopathol Pharmacol. 2000 Sep-Dec;13(3):123-28.
30.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. Jan;74(1):18-20.
31.Garozzo A, Tempera G, Ungheri D, Timpanaro R, Castro A. N-acetyl cysteine synergizes with oseltamivir in protecting mice from lethal influenza infection. Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2):349-54.
32.Ghezzi P, Ungheri D. Synergistic combination of N-acetyl cysteine and ribavirin to protect from lethal influenza viral infection in a mouse model. Int J Immunopathol Pharmacol. 2004 Jan-Apr;17(1):99-102.
33.Jariwalla RJ, Roomi MW, Gangapurkar B, Kalinovsky T, Niedzwiecki A, Rath M. Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids. Biofactors. 2007;31(1):1-15.
34.Deryabin PG, Lvov DK, Botikov AG, et al. Effects of a nutrient mixture on infectious properties of the highly pathogenic strain of avian influenza virus A/H5N1. Biofactors. 2008;33(2):85-97.
35.Reichenberger F, Tamm M. N-acetylcystein in the therapy of chronic bronchitis. Pneumologie. 2002 Dec;56(12):793-7.
36.Sadowska AM, van Overveld FJ, Gorecka D, et al. The interrelationship between markers of inflammation and oxidative stress in chronic obstructive pulmonary disease: modulation by inhaled steroids and antioxidant. Respir Med. 2005 Feb;99(2):241-9.
37.Stav D, Raz M. Effect of N-acetyl cysteine on air trapping in COPD: a randomized placebo-controlled study. Chest. 2009 Aug;136(2):381-6.
38.Foschino Barbaro MP, Serviddio G, Resta O, et al. Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine. Free Radic Res. 2005 Oct;39(10):1111-8.
39.De Benedetto F, Aceto A, Dragani B, et al. Long-term oral n-acetyl cysteine reduces exhaled hydrogen peroxide in stable COPD. Pulm Pharmacol Ther. 2005;18(1):41-7.
40.van Overveld FJ, Demkow U, Gorecka D, de Backer WA, Zielinski J. New developments in the treatment of COPD: comparing the effects of inhaled corticosteroids and N-acetyl cysteine. J Physiol Pharmacol. 2005 Sep;56 Suppl 4:135-42.
41.Cai S, Chen P, Zhang C, Chen JB, Wu J. Oral N-acetyl cysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. Respirology. 2009 Apr;14(3):354-9.
42.Meyer A, Buhl R, Magnussen H. The effect of oral N-acetyl cysteine on lung glutathione levels in idiopathic pulmonary fibrosis. Eur Respir J. 1994 Mar;7(3):431-6.
43.Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005 Nov 24;353(21):2229-42.
44.Tomioka H, Kuwata Y, Imanaka K, et al. A pilot study of aerosolized N-acetyl cysteine for idiopathic pulmonary fibrosis. Respirology. 2005 Sep;10(4):449-55.
45.Cottin V, Cordier JF. Idiopathic pulmonary fibrosis. Presse Med. 2008 Nov;37(11):1581-90.
46.Felton VM, Borok Z, Willis BC. N-acetyl cysteine inhibits alveolar epithelial-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L805-12.
47.Peake J, Suzuki K. Neutrophil activation, antioxidant supplements and exercise-induced oxidative stress. Exerc Immunol Rev. 2004;10:129-41.
48.Quadrilatero J, Hoffman-Goetz L. N-Acetyl-L-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2004 Jul 2;319(3):894-901.
49.Vassilakopoulos T, Karatza MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol. 2003 Mar;94(3):1025-32.
50.Koechlin C, Couillard A, Simar D, et al. Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2004 May 1;169(9):1022-7.
51.Zembron-Lacny A, Szyszka K, Szygula Z. Effect of cysteine derivatives administration in healthy men exposed to intense resistance exercise by evaluation of pro-antioxidant ratio. J Physiol Sci. 2007 Dec;57(6):343-8.
52.Aguiar AS, Jr., Tuon T, Soares FS, da Rocha LG, Silveira PC, Pinho RA. The effect of n-acetyl cysteine and deferoxamine on exercise-induced oxidative damage in striatum and hippocampus of mice. Neurochem Res. 2008 May;33(5):729-36.
53.Quadrilatero J, Hoffman-Goetz L. N-acetyl-l-cysteine protects intestinal lymphocytes from apoptotic death after acute exercise in adrenalectomized mice. Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1664-72.
54.Quadrilatero J, Hoffman-Goetz L. N-acetyl-L-cysteine inhibits exercise-induced lymphocyte apoptotic protein alterations. Med Sci Sports Exerc. 2005 Jan;37(1):53-6.
55.Kruger K, Frost S, Most E, Volker K, Pallauf J, Mooren FC. Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways. Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1518-27.
56.Evans JL, Maddux BA, Goldfine ID. The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal. 2005 Jul-Aug;7(7-8):1040-52.
57.Anuradha CV. Aminoacid support in the prevention of diabetes and diabetic complications. Curr Protein Pept Sci. 2009 Feb;10(1):8-17.
58.Guo Q, Mori T, Jiang Y, et al. Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats. J Hypertens. 2009 Aug;27(8):1664-71.
59.Song D, Hutchings S, Pang CC. Chronic N-acetyl cysteine prevents fructose-induced insulin resistance and hypertension in rats. Eur J Pharmacol. 2005 Jan 31;508(1-3):205-10.
60.Masha A, Manieri C, Dinatale S, Bruno GA, Ghigo E, Martina V. Prolonged treatment with N-acetyl cysteine and L-arginine restores gonadal function in patients with PCO syndrome. J Endocrinol Invest. 2009 Apr 15.
61.Fulghesu AM, Ciampelli M, Muzj G, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002 Jun;77(6):1128-35.
62.Guan D, Xu Y, Yang M, Wang H, Wang X, Shen Z. N-acetyl cysteine and penicillamine induce apoptosis via the ER stress response-signaling pathway. Mol Carcinog. 2010 Jan;49(1):68-74.
63.Li J, Tu HJ, Dai G, et al. N-acetyl cysteine inhibits human signet ring cell gastric cancer cell line (SJ-89) cell growth by inducing apoptosis and DNA synthesis arrest. Eur J Gastroenterol Hepatol. 2007 Sep;19(9):769-74.
64.Yang J, Su Y, Richmond A. Antioxidants tiron and N-acetyl-L-cysteine differentially mediate apoptosis in melanoma cells via a reactive oxygen species-independent NF-kappaB pathway. Free Radic Biol Med. 2007 May 1;42(9):1369-80.
65.Krasnowska EK, Pittaluga E, Brunati AM, et al. N-acetyl-l-cysteine fosters inactivation and transfer to endolysosomes of c-Src. Free Radic Biol Med. 2008 Dec 1;45(11):1566-72.
66.Reliene R, Pollard JM, Sobol Z, Trouiller B, Gatti RA, Schiestl RH. N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals. Mutat Res. 2009 Jun 1;665(1-2):37-43.
67.Balansky R, Ganchev G, Iltcheva M, Steele VE, De Flora S. Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetyl cysteine. Int J Cancer. 2010 Mar 1;126(5):1047-54.
68.Nishikawa-Ogawa M, Wanibuchi H, Morimura K, et al. N-acetyl cysteine and S-methylcysteine inhibit MeIQx rat hepatocarcinogenesis in the post-initiation stage. Carcinogenesis. 2006 May;27(5):982-8.
69.Van Schooten FJ, Besaratinia A, De Flora S, et al. Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers. Cancer Epidemiol Biomarkers Prev. 2002 Feb;11(2):167-75.
70.Ponz de Leon M, Roncucci L. Chemoprevention of colorectal tumors: role of lactulose and of other agents. Scand J Gastroenterol Suppl. 1997;222:72-5.
71.Estensen RD, Levy M, Klopp SJ, et al. N-acetyl cysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. 1999 Dec 1;147(1-2):109-14.
72.Huynh HQ, Couper RT, Tran CD, Moore L, Kelso R, Butler RN. N-acetyl cysteine, a novel treatment for Helicobacter pylori infection. Dig Dis Sci. 2004 Nov-Dec;49(11-12):1853-61.
73.Kim MH, Yoo HS, Kim MY, et al. Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-kappaB signaling in human gastric carcinoma cells. Int J Mol Med. 2007 Apr;19(4):689-97.
74.Zala G, Flury R, Wust J, Meyenberger C, Ammann R, Wirth HP. Omeprazole/amoxicillin: improved eradication of Helicobacter pylori in smokers because of N-acetyl cysteine. Schweiz Med Wochenschr. 1994 Aug 9;124(31-32):1391-7.
75.Gurbuz AK, Ozel AM, Ozturk R, Yildirim S, Yazgan Y, Demirturk L. Effect of N-acetyl cysteine on Helicobacter pylori. South Med J. 2005 Nov;98(11):1095-7.
76.Palmer LA, Doctor A, Chhabra P, et al. S-nitrosothiols signal hypoxia-mimetic vascular pathology. J Clin Invest. 2007 Sep;117(9):2592-601.
77.Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol. 2009 Dec;297(6):L1013-32.
78.Sajkov D, McEvoy RD. Obstructive sleep apnea and pulmonary hypertension. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):363-70.
79.Kaldararova M. Why is pulmonary hypertension so frustrating? Bratisl Lek Listy. 2009;110(9):536-43.
80.Hoshikawa Y, Ono S, Suzuki S, et al. Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. J Appl Physiol. 2001 Apr;90(4):1299-306.
81.Marsden PA. Low-molecular-weight S-nitrosothiols and blood vessel injury. J Clin Invest. 2007 Sep;117(9):2377-80.
82.Lachmanova V, Hnilickova O, Povysilova V, Hampl V, Herget J. N-acetyl cysteine inhibits hypoxic pulmonary hypertension most effectively in the initial phase of chronic hypoxia. Life Sci. 2005 May 27;77(2):175-82.
83.Chuang IC, Liu DD, Kao SJ, Chen HI. N-acetyl cysteine attenuates the acute lung injury caused by phorbol myristate acetate in isolated rat lungs. Pulm Pharmacol Ther. 2007;20(6):726-33.
84.Liu DD, Kao SJ, Chen HI. N-acetyl cysteine attenuates acute lung injury induced by fat embolism. Crit Care Med. 2008 Feb;36(2):565-71.
85.Hildebrandt W, Alexander S, Bartsch P, Droge W. Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity. Blood. 2002 Mar 1;99(5):1552-5.
86.Iturriaga R, Rey S, Del Rio R, Moya EA, Alcayaga J. Cardioventilatory acclimatization induced by chronic intermittent hypoxia. Adv Exp Med Biol. 2009;648:329-35.