L-Cysteinet
Clinical Studies
References
L-Cysteine may be useful in inflammatory conditions, in anti-aging, asthma, alcoholism, chemotherapy, cigarette smoking, diabetes, burns, chemical sensitivity, liver disease, emphysema, psoriasis and Wilson’s disease.
L-Cysteine is a component of insulin, skin, hair and Glutathione....It detoxifies chemicals and has anti-oxidant properties.
Preliminary evidence indicates that L-Cysteine can impair platelet aggregation. It appears to increase synthesis of nitric oxide, a potent inhibitor of platelet function. In patients with human immunodeficiency virus (HIV) disease, L-Cysteine can increase levels of Glutathione. Increased concentration of Glutathione seems to reduce oxidative stress associated with HIV disease and to improve the number and activity of CD4 T-lymphocytes.
- N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells.
- Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.
- Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice.
N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells.
Tozawa K, Okamoto T, Hayashi Y, Sasaki S, Kawai N, Kohri K.
Department of Urology, Nagoya City University Medical School, Nagoya, Japan.
Transcription factor nuclear factor kappaB (NF-kappaB) controls gene expression of a number of genes, including cytokines such as interleukin-6 (IL-6), granulocyte-macrophage (GM)-CSF, and interleukin-8 (IL-8). IL-6 is known to play important roles in the growth of prostate cancer cells, activation of androgen receptor, and prostate-specific protein expression. NF-kappaB is activated by extracellular signals such as proinflammatory cytokines, chemotherapeutic reagents, and radiation. Here we demonstrate that cisplatin (CDDP) and etoposide (VP-16) induce nuclear translocation of NF-kappaB in prostate cancer cell lines, followed by secretion of IL-6. We also demonstrated that the growth of hormone-independent prostate cancer cell lines can be inhibited by the anti-NF-kappaB reagent N-acetyl-L-cysteine (NAC). These observations indicate that NF-kappaB can be a target of new adjuvant therapy against hormone refractory prostate cancer.
PMID: 11942326 [PubMed - indexed for MEDLINE]
Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.
Gillissen A, Nowak D.
Department of Internal Medicine, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany.
Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have both been frequently investigated. Because of its SH group, NAC scavenges H2O2 (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid). Furthermore, NAC can easily be deacetylated to cysteine, an important precursor of cellular glutathione synthesis, and thus stimulate the cellular glutathione system. This is most evident in pulmonary diseases characterized by low glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication and may even be protective against side-effects of mutagenic agents. In addition NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL-1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces bronchial hyperreactivity, and it is known to stimulate cellular surfactant production. In addition, ambroxol has anti-inflammatory properties owing to its inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. For both substances effective anti-oxidant and anti-inflammatory function has been validated when used in micromolar concentrations. These levels are attainable in vivo in humans. This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol.
Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice.
Hsu CC, Yen HF, Yin MC, Tsai CM, Hsieh CH.
Department of Nutritional Science, Chungshan Medical University, Taichung City, Taiwan.
The effects of n-acetyl cysteine (NAC), s-allyl cysteine (SAC), s-ethyl cysteine, s-methyl cysteine and s-propyl cysteine (SPC) activity on Balb/cA mice against diabetic complications were examined. These complications included hyperglycemia, hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. To induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive days. Five cysteine-containing compounds at 1 g/L were added to the drinking water. After intake of the 5 cysteine-containing agents for 4 wk, body weight loss, plasma concentrations of glucose and insulin, and fibronectin levels were improved (P < 0.05) in diabetic mice. The administration of these agents restored the glutathione level (P < 0.05), reduced the loss of catalase and glutathione peroxidase activities in kidney and liver (P < 0.05), and decreased glucose-induced lipid oxidation, as assessed by malondialdehyde formation (P < 0.05). In all diabetic mice, the intake of these agents reduced triglyceride levels in plasma and liver (P < 0.05); however, only NAC, SAC and SPC treatments reduced cholesterol level in liver (P < 0.05). These cysteine-containing agents elevated the activity of 2 fibrinolytic factors, protein C and antithrombin III (P < 0.05). The overexpression of interleukin-6 and tumor necrosis factor-alpha in diabetic mice was suppressed by the intake of the 5 cysteine-containing agents (P < 0.05). Via their antioxidant activities, the 5 compounds effectively improved glycemic control, delayed oxidation damage, downregulated inflammatory cytokines, and enhanced anticoagulant activity in diabetic mice. These data support the multiple roles of these agents as potential protective agents for delaying diabetic deterioration.
PMID: 15570020 [PubMed - indexed for MEDLINE]
References
McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
Ghio S, de Servi S, Perotti R, et al. Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans- effects of N-acetylcysteine administration. Circulation 1992;86:798-802.
De Rosa SC, Zaretsky MD, Dubs JG, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 2000;30:915-29.
van Zandwijk N, Dalesio O, Pastorino U, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst 2000;92:977-86.
Holt S, Goodier D, Marley R, et al. Improvement in renal function in hepatorenal syndrome with N-acetylcysteine. Lancet 1999;353:294-5.
Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev 1998;3:114-27.
Gillissen A, Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med 1998;92:609-23.
Morini M, Cai T, Aluigi MG, et al. The role of the thiol N-acetylcysteine in the prevention of tumor invasion and angiogenesis. Int J Biol Markers 1999;14:268-71.
De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J 1997;10:1535-41.
Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther 1992;52:125-33.
Sekharam M, Trotti A, Cunnick JM, Wu J. Suppression of fibroblast cell cycle progression in G1 phase by N-acetylcysteine. Toxicol Appl Pharmacol 1998;149:210-6.
Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 2000;22:209-21.
Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 1997;156:1897-901.
Weinbroum AA, Rudick V, Ben-Abraham R, Karchevski E. N-acetyl-L-cysteine for preventing lung reperfusion injury after liver ischemia-reperfusion: a possible dual protective mechanism in a dose-response study. Transplantation 2000;69:853-9.
Morgan LR, Donley PJ, Harrison EF, Hunter HL. The control of ifosfamide-induced hematuria with N-acetylcysteine in patients with advanced carcinoma of the lung. Semin Oncol 1982;9:71-4.
Loehrer PJ Sr, Birch R, Kramer BS, et al. Ifosfamide plus N-acetylcysteine in the treatment of small cell and non-small cell carcinoma of the lung: a Southeastern Cancer Study Group Trial. Cancer Treat Rep 1986;70:919-20.
Loehrer PJ, Williams SD, Einhorn LH. N-acetylcysteine and ifosfamide in the treatment of unresectable pancreatic adenocarcinoma and refractory testicular cancer. Semin Oncol 1983;10:72-5.
Anfossi G, Russo I, Massucco P, et al. N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets. Eur J Clin Invest 2001;31:452-61.
Shyu KG, Cheng JJ, Kuan P. Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol 2002;40:1383-8.
Pela R, Calcagni AM, Subiaco S, et al. N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration 1999;66:495-500.
Tepel M, van der Giet M, Statz M, et al. The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial. Circulation 2003;107:992-5.
Munshi NC, Loehrer PJ Sr, Williams SD, et al. Comparison of N-acetylcysteine and mesna as uroprotectors with ifosfamide combination chemotherapy in refractory germ cell tumors. Invest New Drugs 1992;10:159-163.
Oldemeyer JB, Biddle WP, Wurdeman RL, et al. Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography. Am Heart J 2003;146:E23.