The chemistry and biological activities of N-acetylcysteine

Samuni, Yuval; Goldstein, Sara; Dean, Olivia M.; Berk, Michael

doi:10.1016/j.bbagen.2013.04.016

Cited by 876Sulfur Compounds in BiologyRedox biology and oxidative stressDrug-Induced Hepatotoxicity and Protection

The chemistry and biological activities of N-acetylcysteine

Open access

Samuni, Yuval, Goldstein, Sara, Dean, Olivia M., Berk, Michael·2013·Biochimica et Biophysica Acta (BBA) - General Subjects

DOI 10.1016/j.bbagen.2013.04.016

Open this paper in CoChat — free account Open PDF

Abstract

Background N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders.Scope of review The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry.Major conclusions The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3(-) and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis.General significance The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood-brain barrier as well as elucidating its reactions with components of cell signaling pathways.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.bbagen.2013.04.016

Cites

264 of 264 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

N-acetylcysteine acts as a modulator of synaptic glutamate through the cysteine-glutamate exchanger, increases glutathione and oxidative defenses, enhances neurogenesis and mitochondrial function, decreases pro-inflammatory cytokines, and regulates apoptosis.
“NAC acts as a modulator of synaptic glutamate through the cysteine-glutamate exchanger, increases glutathione and oxidative defenses, enhances neurogenesis and mitochondrial function, decreases pro-inflammatory cytokines, and regulates apoptosis [156].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [156]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029 · see citing works
Peroxynitrite oxidation of sulfhydryls.
Radí, R., Beckman, J. S., Bush, K., & Freeman, B. Α. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64313-7 · Cited by 2,499 · see citing works
Regulation of glutathione synthesis
Lu, S. C.-L. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.05.005 · Cited by 2,131 · see citing works
The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid
Aruoma, O. I., Halliwell, B. B., Hoey, B. M., & Butler, J. (1989) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(89)90066-x · Cited by 1,774 · see citing works
Glutathione and its role in cellular functions
Sies, H. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00177-x · Cited by 1,735 · see citing works
Molecular mechanisms of N-acetylcysteine actions
Zafarullah, M., Li, W. Q., Sylvester, J., & Ahmad, M. (2003) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180300001 · Cited by 1,343 · see citing works
Oxidative stress: From basic research to clinical application
Sies, H. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90281-2 · Cited by 1,332 · see citing works
Hormesis defined
Mattson, M. P. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.08.007 · Cited by 1,253 · see citing works
Glutathione, oxidative stress and neurodegeneration
Schulz, J. B., Lindenau, J. H., Seyfried, J., & DICHGANS, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01595.x · Cited by 1,215 · see citing works
Molecular mechanisms of quinone cytotoxicity
O'Brien, P. J. (1991) · Chemico-Biological Interactions · doi:10.1016/0009-2797(91)90029-7 · Cited by 1,031 · see citing works
Regulation of cellular glutathione
Deneke, S. M., & Fanburg, B. L. (1989) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1989.257.4.l163 · Cited by 839 · see citing works
Unraveling the biological roles of reactive oxygen species
Murphy, M. P., Holmgren, A., Larsson, N.-G., Halliwell, B., Chang, C. J., Kalyanaraman, B., Rhee, S. G., Thornalley, P. J., Partridge, L., Gems, D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.010 · Cited by 836 · see citing works
Mitochondrial permeability transition and oxidative stress
Kowaltowski, A. J., Castilho, R. F., & Vercesi, A. E. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02316-x · Cited by 832 · see citing works
Thiordoxin regulates the DNA binding activity of NF-χB by reduction of a disulphid bond involving cysteine 62
Matthews, J. R., Wakasugi, N., Virelizier, J., Yodoi, J., & Hay, R. T. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.15.3821 · Cited by 831 · see citing works
Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide
Winterbourn, C. C., & Metodiewa, D. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00051-9 · Cited by 799 · see citing works
Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse
Baker, D. L., McFarland, K., LAKE, R. W., Shen, H., Tang, X., Toda, S., & Kalivas, P. W. (2003) · Nature Neuroscience · doi:10.1038/nn1069 · Cited by 740 · see citing works
N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency
Atkuri, K. R., Mantovani, J. J., Herzenberg, L. A., & Herzenberg, L. A. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.04.005 · Cited by 721 · see citing works
The oxidative inactivation of mitochondrial electron transport chain components and ATPase.
Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L., & Davies, K. J. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46227-2 · Cited by 713 · see citing works
A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans
Yang, W., & Hekimi, S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000556 · Cited by 630 · see citing works
Gliogenesis and Glial Pathology in Depression
Rajkowska, G., & Miguel-Hidalgo, J. J. (2007) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152707780619326 · Cited by 612 · see citing works
Peroxynitrite reaction with carbon dioxide/bicarbonate. Kinetics and influence on peroxynitrite-mediated oxidations
Denicola, A., Freeman, B. A., Trujillo, M., & Radi, R. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0363 · Cited by 593 · see citing works
Gene expression and the thiol redox state
Arrigo, A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00175-6 · Cited by 511 · see citing works
Skin Permeability In Vivo: Comparison in Rat, Rabbit, Pig and Man
Bartek, M. J., Labudde, J. A., & Maïbach, H. I. (1972) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12538909 · Cited by 511 · see citing works
N-Acetyl Cysteine for Depressive Symptoms in Bipolar Disorder—A Double-Blind Randomized Placebo-Controlled Trial
Berk, M., Copolov, D. L., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., & Bush, A. I. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.04.022 · Cited by 500 · see citing works
Self-citation
Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse
Aoyama, K., Suh, S. W., Hamby, A. M., Liu, J., Chan, W. Y., Chen, Y., & Swanson, R. A. (2006) · Nature Neuroscience · doi:10.1038/nn1609 · Cited by 484 · see citing works
The antioxidants α‐lipoic acid and N ‐acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice
Farr, S. A., Poon, H. F., Dogrukol‐Ak, D., Drake, J., Banks, W. A., Eyerman, E., Butterfield, D. A., & Morley, J. E. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01580.x · Cited by 459 · see citing works
N-Acetylcystei ne: Pharmacological Considerations and Experimental and Clinical Applications
Cotgreave, I. A. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60985-0 · Cited by 441 · see citing works
Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide
Shafirovich, V., & Lymar, S. V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112202099 · Cited by 440 · see citing works
The promise of N-acetylcysteine in neuropsychiatry
Berk, M., Malhi, G. S., Gray, L. J., & Dean, O. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.01.001 · Cited by 434 · see citing works
Self-citation
N ‐acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double‐blind, placebo‐controlled trial
Lai, Z., Hanczko, R., Bonilla, E., Caza, T. N., Clair, B., Bartos, A., Miklossy, G., Jimah, J., Doherty, E., Tily, H., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34502 · Cited by 428 · see citing works
N-Acetylcysteine, a Glutamate Modulator, in the Treatment of Trichotillomania: A Double-blind, Placebo-Controlled Study
Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.60 · Cited by 424 · see citing works
N -acetylcysteine for antioxidant therapy: pharmacology and clinical utility
Dodd, S., Dean, O., Copolov, D. L., Malhi, G. S., & Berk, M. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14728220802517901 · Cited by 413 · see citing works
Self-citation
Chemistry of Peroxynitrites as Compared to Peroxynitrates
Goldstein, S., Lind, J., & Merényi, G. (2005) · Chemical Reviews · doi:10.1021/cr0307087 · Cited by 411 · see citing works
Self-citation
Role of membrane transport in metabolism and function of glutathione in mammals
Bannai, S., & Tateishi, N. (1986) · The Journal of Membrane Biology · doi:10.1007/bf01870891 · Cited by 386 · see citing works
The reduction potential of nitric oxide (NO) and its importance to NO biochemistry
Bartberger, M. D., Liu, W., Ford, E., Miranda, K. M., Switzer, C., Fukuto, J. M., Farmer, P. J., Wink, D. A., & Houk, K. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162095599 · Cited by 384 · see citing works
Evidence that reactive oxygen species do not mediate NF‐κB activation
Hayakawa, M., Miyashita, H., Sakamoto, I., Kitagawa, M., Tanaka, H., Yasuda, H., Karin, M., & Kikugawa, K. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg332 · Cited by 381 · see citing works
Reaction Kinetics for Nitrosation of Cysteine and Glutathione in Aerobic Nitric Oxide Solutions at Neutral pH. Insights into the Fate and Physiological Effects of Intermediates Generated in the NO/O2 Reaction
Wink, D. A., Nims, R. W., Darbyshire, J. F., Christodoulou, D., Hanbauer, I., Cox, G. W., Laval, F., Laval, J., & Cook, J. A. (1994) · Chemical Research in Toxicology · doi:10.1021/tx00040a007 · Cited by 378 · see citing works
Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients
Lavoie, S., Murray, M. M., Deppen, P., Knyazeva, M. G., Berk, M., Boulat, O., Bovet, P., Bush, A. I., Conus, P., Copolov, D., et al. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301624 · Cited by 371 · see citing works
Self-citation
N-acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro.
Mayer, M., & Noble, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7496 · Cited by 371 · see citing works
Kinetics of Nitrosation of Thiols by Nitric Oxide in the Presence of Oxygen
Kharitonov, V. G., Sundquist, A. R., & Sharma, V. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.47.28158 · Cited by 365 · see citing works
Reaction between S-Nitrosothiols and Thiols: Generation of Nitroxyl (HNO) and Subsequent Chemistry
Wong, P. S.-Y., Hyun, J., Fukuto, J. M., Shirota, F. N., DeMaster, E. G., Shoeman, D. W., & Nagasawa, H. T. (1998) · Biochemistry · doi:10.1021/bi973153g · Cited by 363 · see citing works
Clinical Pharmacokinetics of N-Acetylcysteine
Holdiness, M. R. (1991) · Clinical Pharmacokinetics · doi:10.2165/00003088-199120020-00004 · Cited by 359 · see citing works
Mechanism of Action of N-Acetylcysteine in the Protection Against the Hepatotoxicity of Acetaminophen in Rats In Vivo
Lauterburg, B. H., Corcoran, G. B., & Mitchell, J. R. (1983) · Journal of Clinical Investigation · doi:10.1172/jci110853 · Cited by 358 · see citing works
Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points
Flora, S. D., Izzotti, A., D’Agostini, F., & Balansky, R. M. (2001) · Carcinogenesis · doi:10.1093/carcin/22.7.999 · Cited by 351 · see citing works
Reactions of nitrogen dioxide in aqueous model systems: Oxidation of tyrosine units in peptides and proteins
Prütz, W. A., Mönig, H., Butler, J., & Land, E. J. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90780-5 · Cited by 338 · see citing works
Kinetics of the reactions of hypochlorous acid and amino acid chloramines with thiols, methionine, and ascorbate
Peskin, A. V., & Winterbourn, C. C. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00506-2 · Cited by 338 · see citing works
Hypochlorous Acid Interactions with Thiols, Nucleotides, DNA, and Other Biological Substrates
Prütz, W. A. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0322 · Cited by 327 · see citing works
Autoxidation and Neurotoxicity of 6‐Hydroxydopamine in the Presence of Some Antioxidants
Soto‐Otero, R., Méndez‐Álvarez, E., Ameijeiras, Á. H., Muñoz, A., & Labandeira-García, J. L. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741605.x · Cited by 314 · see citing works
A Double-Blind Randomized Controlled Trial of N -Acetylcysteine in Cannabis-Dependent Adolescents
Gray, K. M., Carpenter, M. J., Baker, N. L., DeSantis, S. M., Kryway, E., Hartwell, K. J., McRae-Clark, A. L., & Brady, K. T. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12010055 · Cited by 306 · see citing works
Toxicity of thiols and disulphides: Involvement of free-radical species
Munday, R. (1989) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(89)90147-0 · Cited by 305 · see citing works
Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function.
Bernard, G. R., Lucht, W. D., Niedermeyer, M. E., Snapper, J. R., Ogletree, M. L., & Brigham, K. L. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111386 · Cited by 303 · see citing works
N-Acetyl Cysteine, a Glutamate-Modulating Agent, in the Treatment of Pathological Gambling: A Pilot Study
Grant, J. E., Kim, S. W., & Odlaug, B. L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.11.021 · Cited by 302 · see citing works
A randomized controlled pilot trial of oral N-acetylcysteine in children with autism
Hardan, A. Y., Fung, L. K., Libove, R. A., Obukhanych, T. V., Nair, S., Herzenberg, L. A., Frazier, T. W., & Tirouvanziam, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.014 · Cited by 293 · see citing works
A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation
OH, S., & Lim, S. S. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.07.018 · Cited by 283 · see citing works
A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system
Miranda, K. M., Paolocci, N., Katori, T., Thomas, D. D., Ford, E., Bartberger, M. D., Espey, M. G., Kass, D. A., Feelisch, M., Fukuto, J. M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1430507100 · Cited by 283 · see citing works
N-acetyl-l-cysteine
de Vries, N., & Flora, S. D. (1993) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240531040 · Cited by 274 · see citing works
Protective Effect of N-Acetylcysteine in Tumor Necrosis Factor-α-Induced Apoptosis in U937 Cells: The Role of Mitochondria
Cossarizza, A., Franceschi, C., Monti, D., Salvioli, S., Bellesia, E., Rivabene, R., Biondo, L. A., Rainaldi, G., Tinari, A., & Malorni, W. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1311 · Cited by 273 · see citing works
N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal cells
Ferrari, G. V. D., Yan, C. T., & Greene, L. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-04-02857.1995 · Cited by 270 · see citing works
N-acetylcysteine: multiple clinical applications.
Millea, P. J. (2009) · PubMed · Cited by 265 · see citing works
Pathways of peroxynitrite oxidation of thiol groups
Quijano, C., Álvarez, B., Gatti, R. M., Augusto, O., & Radí, R. (1997) · Biochemical Journal · doi:10.1042/bj3220167 · Cited by 262 · see citing works
The Role of Cystine-Glutamate Exchange in Nicotine Dependence in Rats and Humans
Knackstedt, L. A., LaRowe, S., Mardikian, P., Malcolm, R., Upadhyaya, H., Hedden, S., Markou, A., & Kalivas, P. W. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.040 · Cited by 260 · see citing works
Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine.
Doroshow, J. H., Locker, G. Y., Ifrim, I., & Myers, C. E. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110328 · Cited by 245 · see citing works
Administration of N‐acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke
Khan, M., Sekhon, B., Jatana, M., Giri, S., Gilg, A. G., Sekhon, C., Singh, I., & Singh, A. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20087 · Cited by 245 · see citing works
The pharmacology of nitroxyl (HNO) and its therapeutic potential: Not just the janus face of NO11This review is dedicated to the career of Prof. Herbert T. Nagasawa, a pioneer in the field of HNO chemistry, biochemistry and pharmacology.
Paolocci, N., Jackson, M. I., Lopez, B., Miranda, K. M., Tocchetti, C. G., Wink, D. A., Hobbs, A. J., & Fukuto, J. M. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.11.002 · Cited by 243 · see citing works
Controlled trial of N-acetylcysteine for patients with probable Alzheimer’s disease
Adair, J. C., Knoefel, J. E., & Morgan, N. (2001) · Neurology · doi:10.1212/wnl.57.8.1515 · Cited by 240 · see citing works
Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration
Burgunder, J., Varriale, A., & Lauterburg, B. H. (1989) · European Journal of Clinical Pharmacology · doi:10.1007/bf00609183 · Cited by 233 · see citing works
Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis*
Ritter, C., Andrades, M. E., Reinke, A., Menna-Barreto, S., Moreira, J. C. F., & Dal-Pizzol, F. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000109454.13145.ca · Cited by 233 · see citing works
Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine
Issels, R. D., Nagele, A., Eckert, K.-G., et al. (1988) · Biochemical Pharmacology · doi:10.1016/0006-2952(88)90176-1 · Cited by 232 · see citing works
Kinetics of the reactions of nitrogen dioxide with glutathione, cysteine, and uric acid at physiological pH
Ford, E., Hughes, M., & Wardman, P. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00850-x · Cited by 229 · see citing works
Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells
Chua, C. C., Hamdy, R. C., & Chua, B. H. L. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00115-4 · Cited by 220 · see citing works
Nutritional biochemistry of cellular glutathione
Sen, C. K. (1997) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(97)00113-7 · Cited by 213 · see citing works
Is Cocaine Desire Reduced by N -Acetylcysteine?
LaRowe, S. D., Myrick, H., Hedden, S. L., Mardikian, P. N., Saladin, M. E., McRae‐Clark, A. L., Brady, K. T., Kalivas, P. W., & Malcolm, R. J. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.7.1115 · Cited by 210 · see citing works
N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
Arakawa, M., & Ito, Y. (2007) · The Cerebellum · doi:10.1080/14734220601142878 · Cited by 206 · see citing works
Mechanism of the Nitrosation of Thiols and Amines by Oxygenated • NO Solutions: the Nature of the Nitrosating Intermediates
Goldstein, S., & Czapski, G. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9536680 · Cited by 205 · see citing works
Self-citation
Role of glutathione in prevention of acetaminophen-induced hepatotoxicity by N-acetyl-L-cysteine in vivo: studies with N-acetyl-D-cysteine in mice.
Corcoran, G. B., & Wong, B. K. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)25048-0 · Cited by 202 · see citing works
N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder
Lafleur, D. L., Pittenger, C., Kelmendi, B., Gardner, T., Wasylink, S., Malison, R. T., Sanacora, G., Krystal, J. H., & Coric, V. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0246-6 · Cited by 200 · see citing works
Pulse radiolysis study of sulfhydryl compounds in aqueous solution
Hoffman, M. Z., & Hayon, E. (1973) · The Journal of Physical Chemistry · doi:10.1021/j100627a005 · Cited by 200 · see citing works
Low-dose N -Acetylcysteine Protects Rats against Endotoxin-mediated Oxidative Stress, But High-dose Increases Mortality
Sprong, R. C., Janssen, A. M. L., Aarsman, C. J. M., van Oirschot, J. F. L. M., van der Bruggen, T., & van Asbeck, B. S. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.9508063 · Cited by 189 · see citing works
N‐Acetylcysteine suppresses TNF‐induced NF‐κB activation through inhibition of IκB kinases
Oka, S., Kamata, H., Kamata, K., Yagisawa, H., & Hirata, H. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01464-2 · Cited by 186 · see citing works
The role of glutathione in radiation and drug induced cytotoxicity.
Mitchell, J. B., & Russo, A. (1987) · PubMed · Cited by 185 · see citing works
The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: An open label trial
Berk, M., Dean, O., Cotton, S. M., Gama, C. S., Kapczinski, F., Fernandes, B. S., Kohlmann, K., Jeavons, S., Hewitt, K., Allwang, C., et al. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.06.005 · Cited by 181 · see citing works
Self-citation
Activation of NF-κB by PM10 Occurs via an Iron-Mediated Mechanism in the Absence of IκB Degradation
Jiménez, L. A., Thompson, J., Brown, D. A., Rahman, I., Antonicelli, F. D., Duffin, R., Drost, E., Hay, R. T., Donaldson, K., & MacNee, W. (2000) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2000.8957 · Cited by 180 · see citing works
Peroxynitrite Reaction with the Reduced and the Oxidized Forms of Lipoic Acid: New Insights into the Reaction of Peroxynitrite with Thiols
Trujillo, M., & Radí, R. (2002) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2619 · Cited by 180 · see citing works
An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: A pilot study
Mardikian, P. N., LaRowe, S. D., Hedden, S., Kalivas, P. W., & Malcolm, R. J. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.10.001 · Cited by 179 · see citing works
Uptake of Glutamate and Cystine in C‐6 Glioma Cells and in Cultured Astrocytes
Cho, Y., & Bannai, S. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb05800.x · Cited by 179 · see citing works
Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Bridgeman, M. M. E., Marsden, M. E., MacNee, W., et al. (1991) · Thorax · doi:10.1136/thx.46.1.39 · Cited by 177 · see citing works
The role of glutathione status in the protection against ischaemic and reperfusion damage: Effects of N-acetyl cysteine
Ceconi, C., Curello, S., Cargnoni, A., et al. (1988) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(88)80174-3 · Cited by 174 · see citing works
N-Acetylcysteine in the Prevention of Contrast-Induced Nephropathy
Fishbane, S. N. (2007) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.02590607 · Cited by 173 · see citing works
Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N‐Acetylcysteine
Chen, G., Shi, J., Hu, Z., & Hang, C. (2008) · Mediators of Inflammation · doi:10.1155/2008/716458 · Cited by 170 · see citing works
Activation of NF-kappa B and elevation of MnSOD gene expression by thiol reducing agents in lung adenocarcinoma (A549) cells
Das, K. C., Lewis-Molock, Y., & White, C. W. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.269.5.l588 · Cited by 168 · see citing works
Prevention of PC12 Cell Death byN-Acetylcysteine Requires Activation of the Ras Pathway
Yan, C. Y. I., & Greene, L. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-11-04042.1998 · Cited by 162 · see citing works
N-Acetyl Cysteine Inhibits Induction of No Production By Endotoxin or Cytokine Stimulated Rat Peritoneal Macrophages, C6 Glial Cells and Astrocytes
Pahan, K., Sheikh, F. G., Namboodiri, A. M., & Singh, I. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00137-8 · Cited by 161 · see citing works
Tissue-specific changes of mitochondrial functions in aged rats: Effect of a long-term dietary treatment with N-acetylcysteine
Cocco, T., Sgobbo, P., Clemente, M. T., Lopriore, B., Grattagliano, I., Paola, M. D., & Villani, G. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.11.034 · Cited by 157 · see citing works
N -Acetylcysteine in Combination With Nitroglycerin and Streptokinase for the Treatment of Evolving Acute Myocardial Infarction
Arstall, M. A., Yang, J., Stafford, I., Betts, W. H., & Horowitz, J. D. (1995) · Circulation · doi:10.1161/01.cir.92.10.2855 · Cited by 153 · see citing works
In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds
Flora, S. D., Bennicelli, C., Camoirano, A., Serra, D., Romano, M., Rossi, G. A., Morelli, A. M., & FLORA, A. D. (1985) · Carcinogenesis · doi:10.1093/carcin/6.12.1735 · Cited by 150 · see citing works
The effect of N-acetylcysteine on nuclear factor-κB activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis*
Paterson, R., Galley, H. F., & Webster, N. R. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000089945.69588.18 · Cited by 146 · see citing works
The reaction of superoxide radical with N-acetylcysteine
Benrahmoune, M., Thérond, P., & Abedinzadeh, Z. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00380-4 · Cited by 143 · see citing works
Cytoprotection against Oxidative Stress and the Regulation of Glutathione Synthesis
Dickinson, D. A., Moellering, D. R., Iles, K. E., Patel, R. P., Levonen, A., Wigley, A. F., Darley-Usmar, V. M., & Forman, H. J. (2003) · Biological Chemistry · doi:10.1515/bc.2003.061 · Cited by 141 · see citing works
N-Acetylcysteine Induces Cell Cycle Arrest in Hepatic Stellate Cells through Its Reducing Activity
Kim, K.-Y., Rhim, T., Choi, I., & Kim, S.-S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100975200 · Cited by 140 · see citing works
N‐acetylcysteine prevents loss of dopaminergic neurons in the EAAC1−/− mouse
Berman, A., Chan, W., Brennan, A. M., Reyes, R. C., Adler, B. L., Suh, S. W., Kauppinen, T. M., Edling, Y., & Swanson, R. A. (2010) · Annals of Neurology · doi:10.1002/ana.22162 · Cited by 136 · see citing works
A low molecular weight copper chelator crosses the blood–brain barrier and attenuates experimental autoimmune encephalomyelitis
Offen, D., Gilgun‐Sherki, Y., Barhum, Y., Benhar, M., Grinberg, L. N., Reich, R., Melamed, E., & Atlas, D. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02428.x · Cited by 136 · see citing works
Kinetics and equilibria of thiol/disulfide interchange reactions of selected biological thiols and related molecules with oxidized glutathione
Keire, D. A., Strauss, E. J., Guo, W., Noszál, B., & Rabenstein, D. L. (1992) · The Journal of Organic Chemistry · doi:10.1021/jo00027a023 · Cited by 134 · see citing works
The emergence of nitroxyl (HNO) as a pharmacological agent
Switzer, C., Flores‐Santana, W., Mancardi, D., Donzelli, S., Basudhar, D., Ridnour, L. A., Miranda, K. M., Fukuto, J. M., Paolocci, N., & Wink, D. A. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.04.015 · Cited by 134 · see citing works
Redox regulation of surface protein thiols: Identification of integrin α-4 as a molecular target by using redox proteomics
Laragione, T., Bonetto, V., Casoni, F., Massignan, T., Bianchi, G., Gianazza, E., & Ghezzi, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434516100 · Cited by 132 · see citing works
Hypothiocyanous acid reactivity with low-molecular-mass and protein thiols: absolute rate constants and assessment of biological relevance
Skaff, O., Pattison, D. I., & Davies, M. J. (2009) · Biochemical Journal · doi:10.1042/bj20090276 · Cited by 132 · see citing works
Reactive oxygen species up-regulate CD11b in microglia via nitric oxide: Implications for neurodegenerative diseases
Roy, A., Jana, A., Yatish, K., Freidt, M. B., Fung, Y. K., Martinson, J., & Pahan, K. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.05.026 · Cited by 131 · see citing works
Efficacy of a Vitamin/Nutriceutical Formulation for Moderate-stage to Later-stage Alzheimer's disease: A Placebo-controlled Pilot Study
Remington, R., Chan, A., Paskavitz, J., & Shea, T. B. (2008) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317508325094 · Cited by 129 · see citing works
N‐acetylcysteine – passe‐partout or much ado about nothing?
Aitio, M. (2005) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2005.02523.x · Cited by 125 · see citing works
Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials
Breitkreutz, R., Pittack, N., Nebe, C. T., Schuster, D., Brust, J., Beichert, M., Hack, V., Daniel, V., Edler, L., & Dröge, W. (2000) · Journal of Molecular Medicine · doi:10.1007/s001099900073 · Cited by 124 · see citing works
Kinetics of N-Nitrosation in Oxygenated Nitric Oxide Solutions at Physiological pH: Role of Nitrous Anhydride and Effects of Phosphate and Chloride
Lewis, R. S., Tannenbaum, S. R., & Deen, W. M. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00119a006 · Cited by 123 · see citing works
Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N‐acetylcysteine
Albini, A., D’Agostini, F., Giunciuglio, D., et al. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910610121 · Cited by 122 · see citing works
Antioxidant action via p53-mediated apoptosis.
Liu, M., Pelling, J. C., Ju, J., et al. (1998) · PubMed · Cited by 121 · see citing works
Reactive Oxygen Species Participate in Peroxynitrite-Induced Apoptosis in HL-60 Cells
Lin, K.-T., Xue, J., Sun, F. F., & Wong, P. Y.-K. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.5897 · Cited by 121 · see citing works
Superoxide radical–initiated apoptotic signalling pathway in selenite-treated HepG2 cells: mitochondria serve as the main target
Shen, H.-M., Yang, C.-F., Ding, W.-X., Liu, J., & Ong, C.-N. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00421-4 · Cited by 119 · see citing works
First Steps in the Oxidation of Sulfur-Containing Amino Acids by Hypohalogenation: Very Fast Generation of Intermediate Sulfenyl Halides and Halosulfonium Cations
Armesto, X. L., Canle, M., Fernández, M. I., García, M. V., & Santaballa, J. A. (2000) · Tetrahedron · doi:10.1016/s0040-4020(99)01066-2 · Cited by 118 · see citing works
Estimation and identification of thiols in rat spleen after cysteine or glutathione treatment: Relevance to protection against nitrogen mustards
Ball, C. R. (1966) · Biochemical Pharmacology · doi:10.1016/0006-2952(66)90157-2 · Cited by 116 · see citing works
Effect of N -Acetylcysteine on Mitochondrial Function Following Traumatic Brain Injury in Rats
Xiong, Y., Peterson, P. L., & Lee, C. P. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.1067 · Cited by 114 · see citing works
Glutathione redox pathway and reperfusion injury. Effect of N-acetylcysteine on infarct size and ventricular function.
Forman, M. B., Puett, D. W., Cates, C. U., McCroskey, D. E., Beckman, J. K., Greene, H. L., & Virmani, R. (1988) · Circulation · doi:10.1161/01.cir.78.1.202 · Cited by 113 · see citing works
Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers.
van Schooten, F., Nia, A. B., Nia, A. B., Flora, S. D., D’Agostini, F., Izzotti, A., Camoirano, A., Balm, A. J. M., Dallinga, J. W., Bast, A., et al. (2002) · PubMed · Cited by 111 · see citing works
Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer
Flora, S. D., Izzotti, A., D’Agostini, F., & Cesarone, C. F. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90295-9 · Cited by 110 · see citing works
N‐Acetylcysteine (NAC) in Young Marijuana Users: An Open‐Label Pilot Study
Gray, K. M., Watson, N. L., Carpenter, M. J., & LaRowe, S. D. (2010) · The American Journal on Addictions · doi:10.1111/j.1521-0391.2009.00027.x · Cited by 109 · see citing works
N-Acetylcysteine treatment to prevent the progression of multisystem organ failure
Molnár, Z., Shearer, E., & Lowe, D. (1999) · Critical Care Medicine · doi:10.1097/00003246-199906000-00028 · Cited by 108 · see citing works
Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds
Banner, W., Koch, M., Capin, D., et al. (1986) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(86)90331-5 · Cited by 108 · see citing works
N-acetylcysteine inhibits endothelial cell invasion and angiogenesis.
Cai, T., Fassina, G., Morini, M., et al. (1999) · PubMed · Cited by 106 · see citing works
Thiyl radicals react with nitric oxide to form S-nitrosothiols with rate constants near the diffusion-controlled limit
Madej, E., Folkes, L. K., Wardman, P., Czapski, G., & Goldstein, S. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.02.015 · Cited by 105 · see citing works
Self-citation
How many distinct enzymes are responsible for the several cellular processes involving thiol:protein‐disulphide interchange?
Freedman, R. B. (1979) · FEBS Letters · doi:10.1016/0014-5793(79)80085-x · Cited by 103 · see citing works
N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism
Kharazmi, A., Nielsen, H., & Schiøtz, P. O. (1988) · International Journal of Immunopharmacology · doi:10.1016/0192-0561(88)90148-8 · Cited by 103 · see citing works
Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine.
Winniford, M. D., Kennedy, P. L., WELLS, P. J., et al. (1986) · Circulation · doi:10.1161/01.cir.73.1.138 · Cited by 102 · see citing works
Transforming growth factor beta 1-induced apoptosis in human ovarian carcinoma cells: protection by the antioxidant N-acetylcysteine and bcl-2.
Lafon, C., Mathieu, C., Guerrin, M., Pierre, O., Vidal, S., & Valette, A. (1996) · PubMed · Cited by 102 · see citing works
Effect of N -acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial
Åkerlund, B., Jarstrand, C., Lindeke, B., Sönnerborg, A. B., Åkerblad, A.-C., & Rasool, O. (1996) · European Journal of Clinical Pharmacology · doi:10.1007/s002280050140 · Cited by 100 · see citing works
Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood–brain barrier: Protection by the antioxidant N-acetylcysteine
Erickson, M. A., Hansen, K. M., & Banks, W. A. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.07.003 · Cited by 100 · see citing works
N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA
Oikawa, S. (1999) · Carcinogenesis · doi:10.1093/carcin/20.8.1485 · Cited by 100 · see citing works
N-Acetyl-l-cysteine Enhances Apoptosis through Inhibition of Nuclear Factor-κB in Hypoxic Murine Embryonic Fibroblasts
Qanungo, S., Wang, M., & Nieminen, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406749200 · Cited by 99 · see citing works
N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease
Sadowska, A. M. (2012) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465812437563 · Cited by 99 · see citing works
Suppression of NF-κB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells
Kim, H., Seo, J. Y., Roh, K. H., et al. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00368-3 · Cited by 98 · see citing works
Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24 human bladder cancer cells.
Kawakami, S., Kageyama, Y., Fujii, Y., et al. (2001) · PubMed · Cited by 97 · see citing works
Use of N-acetylcysteine to reduce post-cardiothoracic surgery complications: a meta-analysis
Baker, W. L., Anglade, M. W., Baker, E. L., White, C. M., Kluger, J., & Coleman, C. I. (2009) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/j.ejcts.2008.11.027 · Cited by 97 · see citing works
N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels
Wiklund, O., Fager, G., Andersson, A. D. R., Lundstam, U., Masson, P., & Hultberg, B. L. (1996) · Atherosclerosis · doi:10.1016/0021-9150(95)05635-1 · Cited by 96 · see citing works
N-Acetylcysteine ethyl ester (NACET): A novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential
Giustarini, D., Milzani, A., Dalle‐Donne, I., et al. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.09.010 · Cited by 96 · see citing works
A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence.
Grant, J., Odlaug, B., & Kim, S.-W. (2010) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.06.018 · Cited by 93 · see citing works
Protective effects of N-acetylcysteine treatment post acute paraquat intoxication in rats and in human lung epithelial cells
Yeh, S. T.-Y., Guo, H., Su, Y.-S., et al. (2006) · Toxicology · doi:10.1016/j.tox.2006.03.019 · Cited by 93 · see citing works
Efficacy of N-Acetylcysteine in the Treatment of Nicotine Dependence: A Double-Blind Placebo-Controlled Pilot Study
Schmaal, L., Berk, L., Hulstijn, K. P., Cousijn, J., Wiers, R. W., & van den Brink, W. (2011) · European Addiction Research · doi:10.1159/000327682 · Cited by 93 · see citing works
The metabolism of N-acetylcysteine by human endothelial cells
Cotgreave, I. A., Moldéus, P., & Schuppe, I. (1991) · Biochemical Pharmacology · doi:10.1016/0006-2952(91)90674-t · Cited by 93 · see citing works
No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid.
Cotgreave, I. A., Eklund, A., Larsson, K., & Moldéus, P. (1987) · PubMed · Cited by 93 · see citing works
Role ofN-acetylcysteine and cystine in glutathione synthesis in human erythrocytes
Whillier, S., Raftos, J. E., Chapman, B. E., & Kuchel, P. W. (2009) · Redox Report · doi:10.1179/135100009x392539 · Cited by 92 · see citing works
N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: Relevance to schizophrenia and bipolar disorder
Dean, O. M., van den Buuse, M., Berk, M., Copolov, D., Mavros, C., & Bush, A. I. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.05.027 · Cited by 92 · see citing works
Self-citation
Synergistic induction of DNA strand breakage by cigarette tar and nitric oxide
Yoshie, Y. (1997) · Carcinogenesis · doi:10.1093/carcin/18.7.1359 · Cited by 92 · see citing works
Lipoprotein(a) reduction by N-acetylcysteine
Gavish, D., & Breslow, J. L. (1991) · The Lancet · doi:10.1016/0140-6736(91)92161-t · Cited by 89 · see citing works
N-Acetylcysteine protects against age-related decline of oxidative phosphorylation in liver mitochondria
Miquel, J., Ferrándiz, M. L., de Juan, E., Sevila, I., & Martı́nez, M. (1995) · European Journal of Pharmacology Environmental Toxicology and Pharmacology · doi:10.1016/0926-6917(95)90041-1 · Cited by 88 · see citing works
The oxidizing power of the glutathione thiyl radical as measured by its electrode potential at physiological pH
Madej, E., & Wardman, P. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.002 · Cited by 87 · see citing works
Metabolic studies with acetylcysteine
Sheffner, A. L., Medler, E. M., Bailey, K. R., Gallo, D. G., Mueller, A. J., & Sarett, H. P. (1966) · Biochemical Pharmacology · doi:10.1016/0006-2952(66)90197-3 · Cited by 87 · see citing works
Potential in vivo amelioration by N‐acetyl‐L‐cysteine of oxidative stress in brain in human double mutant APP/PS‐1 knock‐in mice: Toward therapeutic modulation of mild cognitive impairment
Huang, Q.-Z., Aluise, C., Joshi, G., Sultana, R., Clair, D. S., Markesbery, W., & Butterfield, D. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22422 · Cited by 86 · see citing works
Activation of NFκB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells
Murley, J. S., Kataoka, Y., Hallahan, D. E., Roberts, J. C., & Grdina, D. J. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00554-8 · Cited by 86 · see citing works
Oxidant-Antioxidant Balance in Granulocytes During ARDS
Laurent, T., Markert, M., Feihl, F., Schaller, M., & Perret, C. H. (1996) · CHEST Journal · doi:10.1378/chest.109.1.163 · Cited by 85 · see citing works
N-Acetylcysteine Inhibits in Vivo Nitric Oxide Production by Inducible Nitric Oxide Synthase
Bergamini, S., Rota, C., Canali, R., Staffieri, M., Daneri, F., Bini, A., Giovannini, F., Tomasi, A., & Iannone, A. (2001) · Nitric Oxide · doi:10.1006/niox.2001.0356 · Cited by 84 · see citing works
Uptake and distribution of N-acetylcysteine in mice: tissue-specific effects on glutathione concentrations
McLellan, L. I., Lewis, A. D., Hall, D. J., Ansell, J. D., & Wolf, C. R. (1995) · Carcinogenesis · doi:10.1093/carcin/16.9.2099 · Cited by 84 · see citing works
Population, Acid−Base, and Redox Properties ofN-Acetylcysteine Conformers
Noszál, B., Visky, D., & Kraszni, M. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm9909600 · Cited by 83 · see citing works
Influence of ferulic acid on nicotine-induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine
Sudheer, A. R., Muthukumaran, S., Nagarajan, D., Devaraj, H., & Menon, V. P. (2007) · Toxicology · doi:10.1016/j.tox.2007.10.016 · Cited by 83 · see citing works
Effects of age on levels of cysteine, glutathione and related enzyme activities in livers of mice and rats and an attempt to replenish hepatic glutathione level of mouse with cysteine derivatives
Nakata, K., Kawase, M., Ogino, S., et al. (1996) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(96)01771-x · Cited by 79 · see citing works
Leak formation in human erythrocytes by the radical-forming oxidant t-
Deüticke, B., Heller, K. B., & Haest, C. W. M. (1986) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(86)90108-2 · Cited by 79 · see citing works
The effectiveness of N-acetylcysteine in isolated hepatocytes, against the toxicity of paracetamol, acrolein, and paraquat
Dawson, J. R., Norbeck, K., Anundi, I., et al. (1984) · Archives of Toxicology · doi:10.1007/bf00316579 · Cited by 79 · see citing works
N-acetylcysteine increases the glutathione content and protects rat alveolar type II cells against paraquat-induced cytotoxicity
Hoffer, E., Baum, Y., Tabak, A., et al. (1996) · Toxicology Letters · doi:10.1016/0378-4274(95)03446-3 · Cited by 78 · see citing works
N-Acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson's disease
Martı́nez, M. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02005-9 · Cited by 77 · see citing works
Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents.
Steele, V. E., Kelloff, G. J., Wilkinson, B. P., et al. (1990) · PubMed · Cited by 76 · see citing works
Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparison in vitro of some thiol-containing drugs.
Gressier, B., Cabanis, A., Lebegue, S., et al. (1994) · PubMed · Cited by 76 · see citing works
N-acetylcysteine, coenzyme Q10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes
González, R., Ferrín, G., Hidalgo, A. B., Ranchal, I., López‐Cillero, P., González, M. S., López‐Lluch, G., Briceño, J., Gómez‐Bravo, M. Á., Poyato, A., et al. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.06.003 · Cited by 75 · see citing works
N-Acetylcysteine enhances T cell functions and T cell growth in culture
Eylar, E. H., Rivera-Quiñones, C., Molina, C., et al. (1993) · International Immunology · doi:10.1093/intimm/5.1.97 · Cited by 75 · see citing works
Role of reactive oxygen intermediates in the interferon-mediated depression of hepatic drug metabolism and protective effect of N-acetylcysteine in mice.
Ghezzi, P., Bianchi, M., Gianera, L., et al. (1985) · PubMed · Cited by 73 · see citing works
Alteration of immune functions and Th1/Th2 cytokine balance in nicotine-induced murine macrophages: Immunomodulatory role of eugenol and N-acetylcysteine
Mahapatra, S. K., Bhattacharjee, S., Chakraborty, S. P., Majumdar, S., & Roy, S. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2010.12.020 · Cited by 73 · see citing works
Nitric Oxide and N-Acetylcysteine Inhibit the Activation of Mitogen-activated Protein Kinases by Angiotensin II in Rat Cardiac Fibroblasts
Wang, D., Yu, X., & Brecher, P. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.33027 · Cited by 72 · see citing works
Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels
Wang, D., Yu, X., Cohen, R. A., & Brecher, P. I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.12223 · Cited by 71 · see citing works
The platelet as a peripheral marker in psychiatric illness
Plein, H., & Berk, M. (2001) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.251 · Cited by 71 · see citing works
Self-citation
[General Articles] Intracellular Thiol Concentration Modulating Inflammatory Response: Influence on the Regulation of Cell Functions Through Cysteine Prodrug Approach
Santangelo, F. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033456567 · Cited by 70 · see citing works
Protective Effects of N-acetyl-L-cysteine on the Reduction of Dopamine Transporters in the Striatum of Monkeys Treated with Methamphetamine
Hashimoto, K., Tsukada, H., Nishiyama, S., Fukumoto, D., Kakiuchi, T., Shimizu, E., & Iyo, M. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300512 · Cited by 70 · see citing works
Reactive oxygen species‐induced cell death of rat primary astrocytes through mitochondria‐mediated mechanism
Wang, C., Fang, K., Yang, C., & Tzeng, S. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22196 · Cited by 69 · see citing works
Electrochemical evidences in oxidation of acetaminophen in the presence of glutathione and N-acetylcysteine
Shayani‐Jam, H., & Nematollahi, D. (2009) · Chemical Communications · doi:10.1039/b916458h · Cited by 68 · see citing works
N-acetyl-L-cysteine inhibits 26S proteasome function: implications for effects on NF-κB activation
Pajonk, F., Riess, K., Sommer, A., & McBride, W. H. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00743-8 · Cited by 66 · see citing works
Infarct size limitation: Acute N‐acetylcysteine defense (ISLAND trial): Preliminary analysis and report after the first 30 patients
SOCHMAN, J., Vrbská, J., Musilová, B., & Roček, M. (1996) · Clinical Cardiology · doi:10.1002/clc.4960190205 · Cited by 66 · see citing works
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine
Liu, M., Wikonkál, N. M., & Brash, D. E. (1999) · Carcinogenesis · doi:10.1093/carcin/20.9.1869 · Cited by 66 · see citing works
Therapeutic efficacy of aortic administration of N-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model.
Neuwelt, E. A., Pagel, M. A., Hasler, B. P., DeLoughery, T. G., & Muldoon, L. L. (2001) · PubMed · Cited by 65 · see citing works
Gastrointestinal metabolism of N‐acetylcysteine in the rat, including an assay for sulfite in biological systems
Cotgreave, I. A., Berggren, M. I., Jones, T. W. A., et al. (1987) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.2510080408 · Cited by 65 · see citing works
The specificity of platelet glutamate receptor supersensitivity in psychotic disorders
Berk, M., Plein, H., & Belsham, B. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)80002-8 · Cited by 64 · see citing works
Self-citation
N-Acetyl-l-cysteine suppresses TGF-β signaling at distinct molecular steps: The biochemical and biological efficacy of a multifunctional, antifibrotic drug
Meurer, S. K., Lahme, B., Tihaa, L., et al. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.07.001 · Cited by 63 · see citing works
Effects of N-acetylcysteine in the rat heart reperfused after low-flow ischemia: Evidence for a direct scavenging of hydroxyl radicals and a nitric oxide-dependent increase in coronary flow
Brunet, J., Boily, M.-J., Cordeau, S., & Rosiers, C. D. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)00077-b · Cited by 62 · see citing works
VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND MELANOMA. N-ACETYLCYSTEINE DOWNREGULATES VEGF PRODUCTION IN VITRO
Redondo, P., Bandrés, E., Solano, T., Okroujnov, I., & García‐Foncillas, J. (2000) · Cytokine · doi:10.1006/cyto.1999.0566 · Cited by 62 · see citing works
Effects of N-acetyl-cysteine treatment on glutathione depletion and a short-term spatial memory deficit in 2-cyclohexene-1-one-treated rats
Choy, K. H. C., Dean, O. M., Berk, M., Bush, A. I., & van den Buuse, M. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.035 · Cited by 62 · see citing works
Self-citation
The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women
Arranz, L., Fernández, C., Rodríguez, A., Ribera, J. M., & la Fuente, M. D. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.07.014 · Cited by 62 · see citing works
Progressive oxidative membrane damage in erythrocytes after pulse treatment with t-butylhydroperoxide
Deuticke, B., Heller, K. B., & Haest, C. W. M. (1987) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(87)90245-8 · Cited by 62 · see citing works
Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury
Ellis, E. F., Dodson, L. Y., & Police, R. J. (1991) · Journal of neurosurgery · doi:10.3171/jns.1991.75.5.0774 · Cited by 62 · see citing works
Protection by N-acetylcysteine of the histopathological and cytogenetical damage produced by exposure of rats to cigarette smoke
Balansky, R. M., D’Agostini, F., Zanacchi, P., et al. (1992) · Cancer Letters · doi:10.1016/0304-3835(92)90072-4 · Cited by 60 · see citing works
Biological response to phorbol ester determined by alternative G1 pathways.
Huang, T., Duyster, J., & Wang, J. Y. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4793 · Cited by 60 · see citing works
Effects of <scp>N</scp>‐acetyl cysteine on cognitive function in bipolar disorder
Dean, O. M., Bush, A. I., Copolov, D. L., Kohlmann, K., Jeavons, S., Schapkaitz, I., Anderson‐Hunt, M., & Berk, M. (2012) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2012.02392.x · Cited by 58 · see citing works
Self-citation
Determination of absolute rate constants for the reversible hydrogen-atom transfer between thiyl radicals and alcohols or ethers
Schöneich, C., Asmus, K., & Bonifacic, M. (1995) · Journal of the Chemical Society Faraday Transactions · doi:10.1039/ft9959101923 · Cited by 58 · see citing works
Redox Paradox: Effect of N-Acetylcysteine and Serum on Oxidation Reduction–Sensitive Mitogen-Activated Protein Kinase Signaling Pathways
Chan, E. D., Riches, D. W. H., & White, C. W. (2001) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.24.5.4280 · Cited by 58 · see citing works
N-Acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps
Estensen, R. D., Levy, M., Klopp, S. J., et al. (1999) · Cancer Letters · doi:10.1016/s0304-3835(99)00281-5 · Cited by 57 · see citing works
N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death
Zheng, J., Lou, J. R., Zhang, X.-X., Benbrook, D. M., Hanigan, M. H., Lind, S. E., & Ding, W. (2010) · Cancer Letters · doi:10.1016/j.canlet.2010.07.003 · Cited by 57 · see citing works
Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms
Parasassi, T., Brunelli, R., Bracci‐Laudiero, L., Greco, G., Gustafsson, A. C., Krasnowska, E. K., Lundeberg, J., Lundeberg, T., Pittaluga, E., Romano, M.-C., et al. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401663 · Cited by 57 · see citing works
NADH:ubiquinone oxidoreductase from bovine mitochondria. cDNA sequence of a 19 kDa cysteine-rich subunit
Dupuis, A., Skehel, M. J., & Walker, J. E. (1991) · Biochemical Journal · doi:10.1042/bj2770011 · Cited by 56 · see citing works
N-acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice
Cao, L., Li, L., & Zuo, Z. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.044 · Cited by 56 · see citing works
Red blood cell permeability to thiol compounds following oxidative stress
Mazor, D., Golan, E., Philip, V., Katz, M., Jafe, A., Ben‐Zvi, Z., & Meyerstein, N. (1996) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1996.tb01370.x · Cited by 56 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

D.D. Perrin (Ed.), Stability Constants of Metal Ion Complexes, Part B: Organic Ligands, Pergamon Press, Oxford-New York-Toronto-Sydney-Paris-Frankfurt, 1979.

Sorted by citations

Antioxidants can increase melanoma metastasis in mice
Le Gal, K., Ibrahim, M. X., Wiel, C., Sayin, V. I., Akula, M. K., Karlsson, C., Dalin, M. G., Akyürek, L. M., Lindahl, P., Nilsson, J., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aad3740 · Cited by 632 · see citing works
N-Acetylcysteine (NAC): Impacts on Human Health
Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M. D., & Goulart, M. O. F. (2021) · Antioxidants · doi:10.3390/antiox10060967 · Cited by 526 · see citing works
Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review
Deepmala, Slattery, J., Kumar, N., Delhey, L., Berk, M., Dean, O., Spielholz, C., & Frye, R. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.015 · Cited by 463 · see citing works
Self-citation
Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence
Tai, H., Wang, Z., Gong, H., Han, X., Zhou, J., Wang, X., Wei, X., Ding, Y., Huang, N., Qin, J., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1247143 · Cited by 334 · see citing works
Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species–mediated DNA damage
Cameron, A. M., Castoldi, A., Sanin, D. E., Flachsmann, L. J., Field, C. S., Puleston, D. J., Kyle, R. L., Patterson, A. E., Hässler, F., Buescher, J. M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0336-y · Cited by 269 · see citing works
Cognitive remission: a novel objective for the treatment of major depression?
Bortolato, B., Miskowiak, K. W., Köhler, C. A., Maes, M., Fernandes, B. S., Berk, M., & Carvalho, A. F. (2016) · BMC Medicine · doi:10.1186/s12916-016-0560-3 · Cited by 252 · see citing works
Self-citation
Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by N-Acetylcysteine
Corbit, L. H., Chieng, B. C., & Balleine, B. W. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.37 · Cited by 134 · see citing works
N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes
Moazzen, H., Lu, X., Ma, N. L., Velenosi, T. J., Urquhart, B. L., Wisse, L. J., Gittenberger-de Groot, A. C., & Feng, Q. (2014) · Cardiovascular Diabetology · doi:10.1186/1475-2840-13-46 · Cited by 111 · see citing works
Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases
Stanga, S., Caretto, A., Boido, M., & Vercelli, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103719 · Cited by 90 · see citing works
The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders
Bradlow, R. C. J., Berk, M., Kalivas, P. W., Back, S. E., & Kanaan, R. A. (2022) · CNS Drugs · doi:10.1007/s40263-022-00907-3 · Cited by 87 · see citing works
Self-citation
Trichotillomania (hair pulling disorder): Clinical characteristics, psychosocial aspects, treatment approaches, and ethical considerations
França, K., Kumar, A., Castillo, D., Jafferany, M., Hyczy da Costa Neto, M., Damevska, K., Wollina, U., & Lotti, T. (2019) · Dermatologic Therapy · doi:10.1111/dth.12622 · Cited by 51 · see citing works
Composition, Properties and Reactions of Coconut Water
Rethinam, P., & Krishnakumar, V. (2022) · Coconut Water · doi:10.1007/978-3-031-10713-9_4 · Cited by 9 · see citing works
The anti-estrogen receptor drug, tamoxifen, is selectively Lethal to P-glycoprotein-expressing Multidrug resistant tumor cells
Bakadlag, R., Limniatis, G., Georges, G., & Georges, E. (2023) · BMC Cancer · doi:10.1186/s12885-022-10474-x · Cited by 9 · see citing works

Authors: Samuni, Y., Goldstein, S., Dean, O. M., & Berk, M.
Affiliations: Barwon Health (AU)
Hebrew University of Jerusalem (IL)
The Royal Melbourne Hospital (AU)
Corresponding author: Goldstein, Sara
ORCID: Goldstein, Sara
Dean, Olivia M.
Venue: Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher: Elsevier BV
Published: 2013-08
Volume: 1830
Issue: 8
Pages: 4117-4129
ISSN: 0304-4165 (ISSN-L)
DOI: 10.1016/j.bbagen.2013.04.016
OpenAlex: W2119624946
Cited by: 876
References: 264
Citations by year: 2026: 57 · 2025: 66 · 2024: 67 · 2023: 80 · 2022: 79 · 2021: 74 · 2020: 70 · 2019: 77 · 2018: 73 · 2017: 61 · 2016: 61 · 2015: 53 · 2014: 46 · 2013: 10
FWCI: 5.23
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
PubMed (publishedVersion)
Minerva Access (University of Melbourne) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: National Health and Medical Research Council of Australia
Simons Autism Foundation
CRC for Mental Health
Rotary Health
Alfred Deakin Postdoctoral Research Fellowship
Israel Science Foundation (1477)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: N-acetylcysteine, antioxidant activity, thiols, disulfide bond reduction, glutathione synthesis, cysteine precursor, reactive oxygen species, peroxynitrite, superoxide, hydrogen peroxide, hydroxyl radicals, nitrite, heavy metal toxicity, doxorubicin cardiotoxicity, ischemia-reperfusion injury, acute respiratory distress syndrome, bronchitis, chemotherapy toxicity, HIV/AIDS, blood-brain barrier, signal transduction
MeSH terms: Acetylcysteine, Animals, Mental Disorders, Blood-Brain Barrier, Cell Cycle, Cell Membrane, Humans, Signal Transduction, Apoptosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The chemistry and biological activities of N-acetylcysteine

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks