The chemistry and biological activities of N-acetylcysteine

被引:658
作者
Samuni, Yuval [1 ]
Goldstein, Sara [2 ]
Dean, Olivia M. [1 ,3 ,4 ]
Berk, Michael [1 ,3 ,4 ,5 ,6 ]
机构
[1] Deakin Univ, Barwon Hlth, Sch Med, Geelong, Vic 3220, Australia
[2] Hebrew Univ Jerusalem, Inst Chem, Accelerator Lab, IL-91904 Jerusalem, Israel
[3] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia
[4] Univ Melbourne, Royal Melbourne Hosp, Dept Psychiat, Parkville, Vic 3052, Australia
[5] Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia
[6] Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2013年 / 1830卷 / 08期
基金
英国医学研究理事会; 以色列科学基金会;
关键词
N-acetylcysteine; Antioxidant; Glutathione precursor; Redox potential; Disulfide bond; Cell-permeability; ACETYL-L-CYSTEINE; DISULFIDE INTERCHANGE REACTIONS; ENDOTHELIAL GROWTH-FACTOR; ABSOLUTE RATE CONSTANTS; NITRIC-OXIDE SOLUTIONS; MNSOD GENE-EXPRESSION; DNA-BINDING ACTIVITY; BLOOD-BRAIN-BARRIER; KAPPA-B ACTIVATION; THIOL REDOX STATUS;
D O I
10.1016/j.bbagen.2013.04.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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)-O-center dot, (NO2)-N-center dot, CO3 center dot- 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. (c) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:4117 / 4129
页数:13
相关论文
共 265 条
  • [1] Controlled trial of N-acetyleysteine for patients with probable Alzheimer's disease
    Adair, JC
    Knoefel, JE
    Morgan, N
    [J]. NEUROLOGY, 2001, 57 (08) : 1515 - 1517
  • [2] N-acetylcysteine - passe-partout or much ado about nothing?
    Aitio, ML
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2006, 61 (01) : 5 - 15
  • [3] Effect of N-acetylcysteine(NAC) treatment on HIV-1 infection: A double blind placebo controlled trial
    Akerlund, B
    Jarstrand, C
    Lindeke, B
    Sonnerborg, A
    Akerblad, AC
    Rasool, O
    [J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1996, 50 (06) : 457 - 461
  • [4] INHIBITION OF INVASION, GELATINASE ACTIVITY, TUMOR TAKE AND METASTASIS OF MALIGNANT-CELLS BY N-ACETYLCYSTEINE
    ALBINI, A
    DAGOSTINI, F
    GIUNCIUGLIO, D
    PAGLIERI, I
    BALANSKY, R
    DEFLORA, S
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1995, 61 (01) : 121 - 129
  • [5] Aluigi MG, 2000, ANTICANCER RES, V20, P3183
  • [6] Intravenous N-Acetylcysteine in the Prevention of Contrast Media-Induced Nephropathy
    Anderson, Spencer M.
    Park, Zoon H.
    Patel, Ramesh V.
    [J]. ANNALS OF PHARMACOTHERAPY, 2011, 45 (01) : 101 - 107
  • [7] Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse
    Aoyama, K
    Suh, SW
    Hamby, AM
    Liu, JL
    Chan, WY
    Chen, YM
    Swanson, RA
    [J]. NATURE NEUROSCIENCE, 2006, 9 (01) : 119 - 126
  • [8] N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology
    Arakawa, Motoki
    Ito, Yoshihisa
    [J]. CEREBELLUM, 2007, 6 (04) : 308 - 314
  • [9] N-acetylcysteine selectively protects cerebellar granule cells from 4-hydroxynonenal-induced cell death
    Arakawa, Motoki
    Ushimaru, Nobuyuki
    Osada, Nobuhiro
    Oda, Tetsuro
    Ishige, Kumiko
    Ito, Yoshihisa
    [J]. NEUROSCIENCE RESEARCH, 2006, 55 (03) : 255 - 263
  • [10] Distribution of radio-labeled N-acetyl-L-cysteine in Sprague-Dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage
    Arfsten, Darryl P.
    Johnson, Eric W.
    Wilfong, Erin R.
    Jung, Anne E.
    Bobb, Andrew J.
    [J]. CUTANEOUS AND OCULAR TOXICOLOGY, 2007, 26 (02) : 113 - 134