Emine ATAKİŞİ, Birkan TOPÇU, Kezban DALGINLI YILDIZ, CANAN GÜLMEZ, Onur ATAKiŞİ

Acute Effects of N-Acetylcysteine on Total Antioxidant Capacity, Total Oxidant Capacity, Nitric Oxide Level and Gammaglutamyl Transpeptidase Activity in Rabbits

Sistein amino asidinin asetilenmiş türevi olan N-asetilsistein (NAS) mukolitik olarak kullanılan bir moleküldür. Yapılan çalışmada tavşanlara verilen NAS'ın total antioksidan kapasite (TAK), total oksidan kapasite (TOK), nitrik oksit (NO), albumin, globulin, glukoz düzeyleri ve gama glutamil transpeptidaz (GGT) aktivitesi üzerine akut etkilerini araştırmak amaçlanmıştır. Çalışmada 11 adet Yeni Zelanda ırkı tavşan kullanıldı. Denemeye başlamadan önce kontrol değerlerini saptamak için kan numuneleri alındı. Daha sonra tek doz kas içi NAS (100 mg/kg) enjekte edildi ve enjeksiyondan 3, 6 ve 9 saat sonra kan numuneleri alındı. Deneme öncesine göre total antioksidan seviyesi 6. ve 9. saatlerde yüksek (P

Tavşanlarda N-Asetil Sisteinin Total Antioksidan Kapasite, Total Oksidan Kapasite, Nitrik Oksit Düzeyleri ve Gamaglutamil Transpeptidaz Aktivitesi Üzerine Akut Etkileri

N-acetylcysteine (NAC), acetylated derivative of cysteine amino acid, is widely used mucolytic agent. In this study, it was aimed to investigate the acute effects of NAC on total antioxidant capacity (TAC), total oxidant capacity (TOC), nitric oxide (NO), albumin, globulin, glucose levels and gammaglutamyl transpeptidase (GGT) activity. Eleven New Zealand rabbits were used in the study. Blood samples from the rabbits were taken before the start of the experiment to determine control values. NAC (100 mg/kg) was injected to rabbits as intramuscularly. Blood samples were collected from vena auricularis of rabbits at 3rd, 6thand 9th h. While TAC levels were found high (P<0.05) at 6 and 9 h, TOC levels were found low (P<0.05) at 3rd, 6th and 9th h after NAC injection compared to the values before the experiment. NO levels were found low (P<0.001) at 6th and 9th h, GGT activities were found low (P<0.05) at 3rd and 6th h, total protein and albumin levels were found low (P<0.05) at 3rd h after NAC injection compared to values before the experiment. As a result, after intramuscular injection of NAC, plasma TAC levels of rabbits increased, while TOC and NO levels decreased. According to the results, it can be concluded that NAC may show antioxidant effect in a short time. Therefore, NAC could be a good alternative when the antioxidant system needs to be strengthened due to its beneficial properties.

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Schermer T, Chavannes N, Dekhuijzen R, Wouters, E, Muris, J, Akkermans R, van Schayck O, van Weel C: Fluticasone and N- acetylcysteine in primary care patients with COPD or chronic bronchitis. Resp Med, 103, 542-551, 2009. DOI: 10.1016/j.rmed.2008.11.003
Adamy C, Mulder P, Khouzami L, Andrieu-Abadie N, Defer N, Candiani G, Pavoine C, Caramelle P, Souktani R, Le Corvoisier P, Perier M, Kirsch M, Damy T, Berdeaux A, Levade T, Thuillez C, Hittinger L, Pecker F: Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats. J Mol Cell Cardiol, 43, 344-353, 2007. DOI: 10.1016/j.yjmcc.2007.06.010
Lasram MM, Lamine AJ, Dhouib IB, Bouzid K, Annabi A, Belhadjhmida N, Ben Ahmed M, El Fazaa S, Abdelmoula J, Gharbi N: Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life Sci, 107, 50-58, 2014. DOI: 1016/j.lfs.2014.04.033
Galley HF, Howdle PD, Walker BE, Webster NR: The effects of intra- venous antioxidants in patients with septic shock. Free Radical Bio Med, , 768-774, 1997. DOI: 10.1016/S0891-5849(97)00059-2
Aruoma OI, Halliwell B, Hoey BM, Butler J: The Antioxidant Action of N-Acetylcysteine - Its Reaction with Hydrogen-Peroxide, Hydroxyl Radical, Superoxide, and Hypochlorous Acid. Free Radical Bio Med, 6, 593- , 1989. DOI: 10.1016/0891-5849(89)90066-X
Skrzydlewska E, Farbiszewski R: Protective effect of N-acetylcysteine on reduced glutathione, reduced glutathione-related enzymes and lipid peroxidation in methanol intoxication. Drug Alcohol Depen, 57, 61-67, DOI: 10.1016/S0376-8716(99)00040-X
Moldeus P, Cotgreave IA, Berggren M: Lung protection by a thiol- containing antioxidant: N-acetylcysteine. Respiration, 50, 31-42, 1986. DOI: 10.1159/000195086
Schmitt B, Vicenzi M, Garrel C, Denis FM: Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biol, 6, 198-205, DOI: 10.1016/j.redox.2015.07.012
Erel O: A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37, 112-119, DOI: 10.1016/j.clinbiochem.2003.10.014
Erel O: A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111, 2005. DOI: 10.1016/j. clinbiochem. 2005.08.008
Garthwaite J: Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci, 14, 60-67, 1991. DOI: 10.1016/0166-2236 (91)90022-M
Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ: Nitric oxide donors: chemical activities and biological applications. Chem Rev, , 1091-1134, 2002. DOI: 10.1021/cr000040l
Tsikas D, Niemann J, Flentje M, Schwarz A, Tossios P: N-Acetylcysteine (NAC) inhibits renal nitrite and nitrate reabsorption in healthy subjects and in patients undergoing cardiac surgery: Risk of nitric oxide (NO) bioavailability loss by NAC? Int J Cardiol, 177, 30-33, 2014. DOI: 10.1016/j. ijcard.2014.09.109
Bergamini S, Rota C, Canali R, Staffieri M, Daneri F, Bini A, Giovannini F, Tomasi A, Iannone A: N-acetylcysteine inhibits in vivo nitric oxide production by inducible nitric oxide synthase. Nitric Oxide, 5, 349-360, DOI: 10.1006/niox.2001.0356
Rocksen D, Lilliehook B, Larsson R, Johansson T, Bucht A: Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. Clin Exp Immunol, 122, 249-256, 2000. DOI: 10.1046/j.1365-2249.2000.01373.x
Lushchak VI: Glutathione homeostasis and functions: Potential targets for medical interventions. J Amino Acids, 2012, Article ID: 736837- , 2012. DOI: 10.1155/2012/736837
Miranda KM, Espey MG, Wink DA: A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5, 71, 2001. DOI: 10.1006/niox.2000.0319
Sener G, Tosun O, Sehirli AO, Kacmaz A, Arbak S, Ersoy Y, Ayanoglu- Dulger G: Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion. Life Sci, 72, 2707-2718, 2003. DOI: 1016/S0024-3205(03)00187-5
Cenesiz S, Ciftci G, Gulbahar MY, Yarim GF, Nisbet HO, Kabak Y, Nisbet C: Investigation of the effects of N-acetyl cysteine and resveratrol to acute phase response in rats with experimentally induced arthritis. Kafkas Univ Vet Fak Derg, 18, 991-996, 2012. DOI: 10.9775/kvfd. 6900
Cotgreave IA: N-acetylcysteine: Pharmacological considerations and experimental and clinical applications. Adv Pharmacol, 38, 205-227, 1997. DOI: 10.1016/S1054-3589(08)60985-0
Berk M, Malhi GS, Gray LJ, Dean OM: The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci, 34, 167-177, 2013. DOI: 10.1016/ j.tips.2013.01.001
Khanna S, Mitra S, Lakhera PC, Khandelwal S: N-acetylcysteine effectively mitigates cadmium-induced oxidative damage and cell death in Leydig cells in vitro. Drug Chem Toxicol, 39, 74-80, 2016. DOI: 3109/01480545.2015.1028068
Jones AL: Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: A critical review. J Toxicol, 36, 277-285, 1998. DOI: 10.3109/15563659809028022
Angulo P, Lindor KD: Treatment of non-alcoholic steatohepatitis. Best practice & research. Clin Gastroenterol, 16, 797-810, 2002. DOI: 1053/bega.2002.0327
Tsuji F, Miyake Y, Aono H, Kawashima Y, Mita S: Effects of bucillamine and N-acetyl-L-cysteine on cytokine production and collagen-induced arthritis (CIA). Clin Exp Immunol, 115, 26-31, 1999. DOI: 10.1046/j.1365- 1999.00749.x
Zhu J, Yin R, Shao H, Dong G, Luo L, Jing H: N-acetylcysteine to ameliorate acute renal injury in a rat cardiopulmonary bypass model. J Thorac Cardiovasc Surg, 133, 696-703, 2007. DOI: 10.1016/j.jtcvs.2006.09.046
Altinoz E, Turkoz Y, Vardi N: The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues. Bratisl Lek Listy, 116, 252-258, 2015. DOI: 10.4149/BLL_2015_049
Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Kuralay E, Ozal E, Demirkilic U, Oz BS, Sayal A, Tatar H: Do N-acetylcysteine, beta-glucan, and coenzyme Q10 mollify myocardial ischemia-reperfusion injury? Heart Surg Forum, 10, 222-227. 2007. DOI: 10.1532/HSF98.20061195
Lee JH, Jo YH, Kim K, Lee JH, Rim KP, Kwon WY, Suh GJ, Rhee JE: Effect of N-acetylcysteine (NAC) on acute lung injury and acute kidney injury in hemorrhagic shock. Resuscitation, 84, 121-127, 2013. DOI: 1016/j.resuscitation.2012.05.017
Groves JT, Wang CC: Nitric oxide synthase: models and mechanisms. Curr Opin Chem Biol, 4, 687-695, 2000. DOI: 10.1016/S1367-5931(00)00146-0
Boga M, Discigil B, Ozkisacik EA, Gurcun U, Badak MI, Dikicioglu E, Yenisey C, Meteoglu I: The combined effect of iloprost and N- acetylcysteine in preventing spinal cord ischemia in rabbits. Eur J Vasc Endovasc Surg, 31, 366-372, 2006. DOI: 10.1016/j.ejvs.2005.10.027
Mansour HH, Hafez HF, Fahmy NM, Hanafi N: Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Bioch Pharmacol, 75, 773-780, 2008. DOI: 10.1016/j. bcp.2007.09.018
Ali MH, Messiha BA, Abdel-Latif HA: Protective effect of ursode- oxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats. Pharm Biol, 1, 1-11, 2015. DOI: 10.3109/13880209.2015.1060247
Levasseur R, Barrios R, Elefteriou F, Glass DA, Lieberman MW, Karsenty G: Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice. Endocrinology, 144, 2761-2764, 2003. DOI: 1210/en.2002-0071
Zhang H, Forman HJ, Choi J: Gamma-glutamyl transpeptidase in glutathione biosynthesis. Methods Enzymol, 401, 468-483, 2005. DOI: 1016/S0076-6879(05)01028-1