N-asetil-L-Sisteinin Ekstramukolitik Etkileri

N-asetil-L-sistein, mukolitik ve ekspektoran etkisi oldukça belirgin bir solunum sistemi ilacıdır. Bu etkileri sayesinde solunum sistemi enfeksiyonlarında sıklıkla reçete edilmektedir. Yapılan araştırmalarda ise N-asetil-L-sisteinin solunum sistemi dışında birçok vakada faydalı etkileri belirlenmiştir. Bu derlemede N-asetil-L-sisteinin kullanıldığı farklı hastalıklar ve farklı etki mekanizmaları hakkında bilgi verilmiştir. Özellikle merkezi sinir sistemi ve antioksidan etkilerinin sayesinde klinikte birçok hastalıkta kullanılabileceği ve asıl tedaviye destek amaçlı kullanılabileceği anlatılmıştır.

Anahtar Kelimeler:

N-asetil-L-sistein, ekstramukolitik

PDF

___

1. Dhar R. (2013). Role of mucolytics in wet cough. J Assoc Physicians India. 61: 23-27.
2. Malerba M, Ragnoli B. (2008). Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Met. 4(8): 1119-1129.
3. Kayaalp O. (1995). Tıbbi Farmakoloji Bölüm 5: Solunum sistemi ile İlgili Bazı İlaçlar. 7. baskı. 1558-1563. Feryal Matbaacılık San ve Tic. Ltd. Şti. Ankara.
4. Samuni Y, Goldstein S, Dean OM, Berk M. (2013). The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta (BBA)-General Subjects. 1830 (8): 4117-4129.
5. EMA. http://www.ema.europa.eu/docs/en_GB/document_library/ Maximum_Residue_Limits Report/2009/11/WC500009290.pdf. Erişim tarihi:10.05.2017.
6. Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. (2014). N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain and behavior. 4(2): 108-122.
7. Echevarria MAN, Reis TA, Capatti GR et al. (2017). N-acetylcysteine for treating cocaine addiction–A systematic review. Psychiatry Research. 251: 197–203
8. Moussawi K, Pacchioni A, Moran M et al. (2009). N-Acetylcysteine reverses cocaine-induced metaplasticity. Nat. Neurosci. 12(2): 182-189.
9. Dean O, Giorlando F, Berk M. (2011). N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. JPN. 36(2): 78.
10. Heard K, Green J. (2012). Acetylcysteine therapy for acetaminophen poisoning. Curr Pharm Biotechnol. 13(10): 1917-1923.
11. Ritter C, Andrades ME, Reinke A et al. (2004). Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Critical care medicine. 32(2): 342-349.
12. Feldman L, Sherman RA, Weissgarten J. (2012). N-Acetylcysteine Use for Amelioration of Aminoglycoside Induced Ototoxicity in Dialysis Patients. Semin Dial. 25(5): 491-494.
13. Garcia-Prats AJ, Schaaf HS, Hesseling AC. (2016). The safety and tolerability of the second-line injectable antituberculosis drugs in children. Expert Opinion on Drug Safety. 15(11): 1491-1500.
14. Dhouib IE, Jallouli M, Annabi A et al. (2016) A minireview on N-acetylcysteine: An old drug with new approaches. Life sciences. 151: 359-363.
15. Gu WJ, Wu ZJ, Wang PF, Aung LHH, Yin RX. (2012). N-Acetylcysteine supplementation for the prevention of atrial fibrillation after cardiac surgery: a meta-analysis of eight randomized controlled trials. BMC Cardiovasc Disord. 12(1): 10.
16. Liu XH, Xu CY, Fan GH. (2014). Efficacy of N-acetylcysteine in preventing atrial fibrillation after cardiac surgery: a meta-analysis of published randomized controlled trials. BMC Cardiovasc Disord. 14(1): 52.
17. Colak N, Nazli Y, Alpay MF et al. (2013). Effect of topical N-acetylcysteine in the prevention of postoperative pericardial adhesion formation in a rabbit model. Cardiovascular Pathology. 22(5): 368-372.
18. Masha A, Martina V. (2014). Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine. Curr Med Chem. 21(32): 3616-3635.
19. Amaral EP, Conceição EL, Costa DL et al. (2016). N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions. BMC microbiology. 16(1): 251.
20. Dasenbrook EC Chmiel JF. (2017). Anti-Inflammatory Therapies for Cystic Fibrosis, in Treatment of Cystic Fibrosis and Other Rare Lung Diseases. Springer. 139-151.
21. Cazzola M, Calzetta L, Facciolo F, Rogliani P, Matera MG. (2017). Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation. Respiratory Research. 18(1): 26.
22. Dekhuijzen P. (2004). Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J 23(4): 629-636.
23. Atalay F, Odabasoglu F, Halici M et al. (2016). N-Acetyl Cysteine Has Both Gastro-Protective and AntiInflammatory Effects in Experimental Rat Models: Its Gastro-Protective Effect is Related to its in Vivo and in Vitro Antioxidant Properties. J Cell Biochem. 117(2): 308-319.
24. Shi X, Li D, Deng Q et al. (2016). Acetoacetic acid induces oxidative stress to inhibit the assembly of very low density lipoprotein in bovine hepatocytes. J Dairy Res. 83(4): 442-446.
25. Slattery J, Kumar N, Delhey L et al. (2015). Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev 55: 294-321.
26. Miyake N, Miyamoto S. (2016). Effectiveness of N-acetylcysteine in the treatment of schizophrenia. Nihon shinkei seishin yakurigaku zasshi. J Clin Psychopharmacol. 36(2): 29.
27. Zavodnick AD, Ali R. (2014). N-Acetylcysteine and metabotropic glutamate receptors: implications for the treatment of schizophrenia: a literature review. Psychiatric Quarterly. 85(2): 177-185.
28. Farokhnia M, Azarkolah A, Adinehfar F et al. (2013). N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 36(6): 185-192.
29. Santos P, Herrmann AP, Benvenutti R et al. (2017). Anxiolytic properties of N-acetylcysteine in mice. Behavioural brain research. 317: 461-469.
30. Mocelin R, Herrmann AP, Marcon M et al. (2015). N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish. Pharmacology Biochemistry and Behavior. 139: 121-126.
31. Berk M, Dean OM, Cotton SM et al. (2014). The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. The Journal of clinical psychiatry. 75(6): 628-636.
32. Oliver G, Dean O, Camfield D et al. (2015). N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 13(1): 12-24.
33. Minarini A, Ferrari S, Galletti M et al. (2017). N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects. Expert Opin Drug Metab Toxicol. 13(3): 279-292.
34. Martínez-Banaclocha M. (2016). Cysteine Network (CYSTEINET) Dysregulation in Parkinson’s Disease: Role of N-acetylcysteine. Curr Drug Metab. 17(4): 368-385.
35. Botsakis K, Theodoritsi S, Grintzalis K et al. (2016). 17β-Estradiol/N-acetylcysteine interaction enhances the neuroprotective effect on dopaminergic neurons in the weaver model of dopamine deficiency. Neuroscience. 320: 221-229.
36. Thakker D, Raval A, Patel L, Walia, R. (2015). N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. Article ID: 817849.
37. Saha L, Kaur S, Saha PK. (2013). N-acetyl cysteine in clomiphene citrate resistant polycystic ovary syndrome: A review of reported outcomes. JPP. 4(3): 187.
38. Tras B, Dinc DA, Uney K. (2014). The effect of N-acetylcysteine on the treatment of clinical endometritis and pregnancy rate in dairy cows. Eurasian J Vet Sci 30(3): 133-137.
39. Gores-Lindholm AR, LeBlanc MM, Causey R et al. (2013). Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance. Theriogenology. 80(3): 218-227.
40. Chen N, Aleksa K, Woodland C, Rieder M, Koren G. (2007). Prevention of ifosfamide nephrotoxicity by N-acetylcysteine: clinical pharmacokinetic considerations. Can J Clin Pharmacol. 14: e246-e250.
41. Miner SE, Dzavik V, Nguyen-Ho P et al. (2004). N-acetylcysteine reduces contrast-associated nephropathy but not clinical events during long-term follow-up. Am Heart J. 148(4): 690-695.
42. Anderson SM, Park ZH, Patel RV. (2011). Intravenous N-acetylcysteine in the prevention of contrast media-induced nephropathy. Ann Pharmacother. 45(1): p. 101-107.
43. Tepel M, Van Der Giet M, Schwarzfeld C. (2000). Prevention of radiographic-contrast-agent–induced reductions in renal function by acetylcysteine. N Engl J Med 343(3): 180-184.
44. Wu MY, Hsiang HF, Wong CS. (2013). The effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy in patients undergoing contrast-enhanced computed tomography: a meta-analysis of randomized controlled trials. Int Urol Nephrol 45(5): 1309-1318.
45. Subramaniam RM, Suarez-Cuervo C, Wilson RF. (2016). Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy A Systematic Review and Meta-analysis. Ann Intern Med. 164(6): 406-416.
46. Hoffmann U, Fischereder M, Krüger B, Drobnik W, Krämer BK. (2004). The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable. J Am Soc Nephrol. 15(2): 407-410.
47. Ozdil B, Cosar A, Akkiz H, Sandikci M, Kece C. (2011). New therapeutic option with N-acetylcysteine for primary sclerosing cholangitis: two case reports. Am J Ther 18(3): e71-e74.
48. Hou Y, Wang L, Yi D, Wu G. (2014). N-acetylcysteine and intestinal health: a focus on its mechanism of action. Frontiers in bioscience (Landmark edition). 20: 872-891.
49. Dabirmoghaddam P, Amali A, Langroudi MM et al. (2013). The Effect of N-Acetyl Cysteine on Laryngopharyngeal Reflux. Acta Medica Iranica. 51(11): 757.
50. Neale JR, James S, Callaghan J, Patel P. (2013). Premedication with N-acetylcysteine and simethicone improves mucosal visualization during gastroscopy: a randomized, controlled, endoscopist-blinded study. Eur J Gastroenterol Hepatol. 25(7): 778-783.
51. Chen MJ, Wang HY, Chang CW. (2013). The add-on N-acetylcysteine is more effective than dimethicone alone to eliminate mucus during narrow-band imaging endoscopy: a double-blind, randomized controlled trial. Scand J Gastroenterol. 48(2): 241-245.
52. Wrotek S, Jędrzejewski T, Piotrowski J, Kozak W. (2016). N-Acetyl-l-cysteine exacerbates generation of IL-10 in cells stimulated with endotoxin in vitro and produces antipyresis via IL-10 dependent pathway in vivo. Immunology Letters. 177: 1-5.
53. Prauchner CA. (2016). Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy. Burns. 43 (3): 471-485.
54. García A, Salas-Jara MJ, Herrera C, González C. (2014). Biofilm and Helicobacter pylori: from environment to human host. World J Gastroenterol. 20(19): 5632-5638.
55. Leite B, Gomes F, Teixeira P et al. (2013). Staphylococcus epidermidis biofilms control by N-acetylcysteine and rifampicin. Am J Ther. 20(4): 322-328.
56. Dinicola S, De Grazia S, Carlomagno G, Pintucci JP. (2014). N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci. 18(19): 2942-8.
57. Aslam S, Darouiche RO. (2011). Role of antibiofilm-antimicrobial agents in control of device-relate infections. Int J Artif Organs. 34(9): 752.
58. Kashef N, Karami S, Djavid GE. (2015). Phototoxic effect of hypericin alone and in combination with acetylcysteine on Staphylococcus aureus biofilms. Photodiagnosis Photodyn Ther. 12(2):186-192.
59. Blasi F, Page C, Rossolini GM et al. (2016). The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 117:190-197.
60. May ER, Conklin KA, Bemis DA. (2016). Antibacterial effect of N-acetylcysteine on common canine otitis externa isolates. Vet Dermatol. 27(3): 188-e47.
61. Olofsson AC, Hermansson M, Elwing H. (2005). Use of a quartz crystal microbalance to investigate the antiadhesive potential of N-acetyl-L-cysteine. Appl Environ Microbiol. 71(5): 2705-2712.
62. Zheng CH, Ahmed K, Rikitomi N, Martinez G, Nagatake T. (1999). The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells. Microbiol Immunol. 43(2): 107-113.
63. Riise GC, Qvarfordt I, Larsson S, Eliasson V, Andersson BA. (2000). Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration. 67(5): 552-558.
64. Homa M, Galgóczy L, Tóth E et al. (2016). In vitro susceptibility of Scedosporium isolates to N-acetyl-L-cysteine alone and in combination with conventional antifungal agents. Med Mycol. 54 (7): 776-779.
65. Geiler J, Michaelis M, Naczk P et al. (2010). 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. 79(3): 413-420.
66. Lasram MM, Dhouib IB, Annabi A, El Fazaa S, Gharbi N. (2015). A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin Biochem. 48(16): 1200-1208.
67. AlMatar M, Batool T, Makky EA. (2016). Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defects. Curr Drug Metab. 17(2): 156-167.