Effects of L-2-oxоthiazolidine-4-carboxylic acid on the lung antioxidant defense system in an asthma mouse model

We aim ed to study the effect of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the lung antioxidant defense system in an animal asthma model. Materials and methods: The study was carried out on 24 female C57BL/6 mice. The mice were divided into 4 treatment groups: group 1 - control group; group 2 - injected with ovalbumin (OVA) and given an OVA inhalant; group 3 - treated with OTCA and phosphate-buffered saline inhalant; and group 4 -injected with OVA and OTCA and given an OVA inhalant. Under sodium pentobarbital anesthesia the animals were killed by exsanguination 48 h after the last inhalation to obtain a lung homogenate. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) and the content of nonprotein sulfhydryl (NPSH) groups in lung homogenate were investigated. Results: OVA decreased the activities of SOD (P = 0.007), CAT (P = 0.004), and GP (P = 0.05) and the NPSH content (P = 0.0008) in the lung homogenate compared with the control animals. Treatment with OVA and OTCA (group 4) resulted in a significant increase in the activities of CAT (P = 0.01) and GP (P = 0.05) and the NPSH content (P = 0.002) compared to the OVA group (group 2). Conclusion: OTCA (160 mg/kg) restored the activities of basic enzymes in the lung antioxidant defense system in an OVA-induced asthma mouse model 48 h after the last nebulization.

Effects of L-2-oxоthiazolidine-4-carboxylic acid on the lung antioxidant defense system in an asthma mouse model

We aim ed to study the effect of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the lung antioxidant defense system in an animal asthma model. Materials and methods: The study was carried out on 24 female C57BL/6 mice. The mice were divided into 4 treatment groups: group 1 - control group; group 2 - injected with ovalbumin (OVA) and given an OVA inhalant; group 3 - treated with OTCA and phosphate-buffered saline inhalant; and group 4 -injected with OVA and OTCA and given an OVA inhalant. Under sodium pentobarbital anesthesia the animals were killed by exsanguination 48 h after the last inhalation to obtain a lung homogenate. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) and the content of nonprotein sulfhydryl (NPSH) groups in lung homogenate were investigated. Results: OVA decreased the activities of SOD (P = 0.007), CAT (P = 0.004), and GP (P = 0.05) and the NPSH content (P = 0.0008) in the lung homogenate compared with the control animals. Treatment with OVA and OTCA (group 4) resulted in a significant increase in the activities of CAT (P = 0.01) and GP (P = 0.05) and the NPSH content (P = 0.002) compared to the OVA group (group 2). Conclusion: OTCA (160 mg/kg) restored the activities of basic enzymes in the lung antioxidant defense system in an OVA-induced asthma mouse model 48 h after the last nebulization.

___

  • Lukacs NW. Cytokines in allergic eosinophilic airway infl ammation. Biol Signals 1996; 5: 209-14.
  • Wild JS, Sur S. CpG oligonucleotide modulation of allergic infl ammation. Allergy 2001; S6: 365-76. 3. Beasley R, Crane J, Lai CK, Pearce N. Prevalence and etiology of asthma. J Allergy Clin Immunol 2000; 105: 466-72.
  • Crystal RJ. Oxidants and respiratory tract epithelial injury: pathogenesis and strategies for therapeutic intervention. Am J Med 1991; 91: S39-S44. 5. MacPherson JC, Comhair SA, Erzurum SC, Klein DF, Lipscomb MF, Kavuru MS et al. Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma: characterization of pathways available to eosinophils for generating reactive nitrogen species. J Immunol 2001; 166: 57 63-72.
  • Dworski R. Oxidant stress and asthma. Th orax 2000; 55: S51-S53.
  • Nadeem A, Chhabra SK, Massod A, Raj HG. Increased oxidative stress and altered levels of antioxidants in asthma. J Allergy Clin Immunol 2003; 111: 72-8.
  • Blesa S, Cortijo J, Martinez-Losa M, Mata M, Seda E, Santangelo F et al. Eff ectiveness of oral N-acetylcysteine in a rat experimental model of asthma. Pharmacol Res 2002; 45: 135-40.
  • MacNee W. Oxidative stress and lung infl ammation in airways disease. Eur J Pharmacol 2001; 429: 195-207.
  • Masella R, Di Benedetto R, Vari R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 2005; 16: 577-86.
  • van der Vliet A, O’NeillCA, CrossCE, KoostraJM, Volz WG, HalliwellB et al. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fl uids. Am J Physiol 1999; 276: L289-L296.
  • Porta P, AebiS, Summer K, LauterburgBH. L-2-oxothiazolidine- 4-carboxylic acid, a cysteine prodrug: pharmacokinetics and eff ects on thiols in plasma and lymphocytes in human. J Pharmacol Exp Th er 1991; 25: 331-4.
  • Oiry J, Puy JY,MialocqP, Clayette P, Fretier P, Jaccard Pet al. Synthesis and in vitro anti-HIV activity in human monocyte- derived macrophages of 2-oxothiazolidine-4(R)-carboxylic acid derivates. J Med Chem 1999; 42: 4733-40.
  • Maral I, Puget K, Michelson H. Comparative study of SOD, catalase and GSH-Px levels in erythrocytes of diff erent animals. Biochem Biophys Res Commun 1977; 77: 1532-5.
  • Koroljuk MA, Ivanova LI, Maiorova IG, Tokarev VE. A method of determining catalase activity. Lab Delo 1988; 1: 16-9 (in Russian).
  • Pereslegina IA. Salivary antioxidant enzymes activity in normal children. Lab Delo 1989; 11: 20-3 (in Russian).
  • DeLucia AJ, Mustafa MG, Hussain MZ, Cross CE. Ozone interaction with rodent lung. III. Oxidation of reduced glutathione and formation of mixed disulfi des between protein and nonprotein sulfh ydryls. J Clin Invest 1975; 55: 794-802.
  • Emelyanov A, Fedoseev G, Abulimity A, Rudinski K, Fedoulov A, Karabanov A et al. Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients. Chest 2001; 120: 1136-9.
  • Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T et al. Airway cytokine expression measured by means of protein array in exhaled breath condensate. Correlation with physiologic properties in asthmatic patients. J Allergy Clin Immunol 2006; 118: 84-90.
  • Fukagawa NK, Hercules E, Ajami AM.L-2-[13C]oxothiazolidine- 4-carboxylic acid: a probe for precursor mobilization for glutathione synthesis. Am J Physiol Endocrinol Metab 2000; 278: E171-E176.
  • Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983; 52: 711-60.
  • Meister A, Anderson ME, Hwang O. Intracellular cysteine and glutathione delivery systems. J Am Coll Nutr 1986; 5: 137-51.
  • Brown LA, Perez JA, Harris FL, Clark RH. Glutathione supplements protect preterm rabbits from oxidative lung injury. Am J Physiol 1996; 270: L446-L451.
  • Mesina JE, Page RH, Hetzel FW, Chopp M. Administration of L-2-oxothiazolidine-4-carboxylate increases glutathione levels in rat brain. Brain Res 1989; 478: 181-3.
  • Lee KS, Kim SR, Park SJ, MinKH, LeeKY, JinSM et al. Antioxidant down-regulates interleukin-18 expression in asthma. Mol Pharmacol 2006; 70: 1184-93.
  • Lee YC, Lee KS, Park SJ, Park HS, Lim JS, Park KH et al. Blockade of airway hyperresponsiveness and infl ammation in a murine model of asthma by a prodrug of cysteine, L-2- oxothiazolidine-4-carboxylic acid. FASEB J 2004; 18: 1917-19.
  • Lee KS, Park HS, Park SJ, Kim SR, Min KH, Jin SM et al. A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma. Mol Pharmacol 2005; 68: 1281-90.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Limb remote ischemic postconditioning is effective but also time-course-limited in protecting the brain from I/R injury

Chenju YI, Haidong GUO, Qiangqiang LIU, Li WANG, Hongxia LI, Ce XU

Is the six-minute walk test correlated with disease control and quality of life in children with asthma?

Özge YILMAZ, Hasan YÜKSEL, Ayhan SÖĞÜT, Bülent GÖKŞEN, Senem ÜSTÜN

Long-term results of pancreaticoduodenectomy and endoscopic resection in the treatment of early stage carcinoma of the ampulla of Vater: case series and review of the literature

Hasan ÖZKAN, Mustafa YAKUT, Gökhan KABAÇAM, Abdulkadir DÖKMECİ, Necati ÖRMECİ

The effects of stobadine on purine metabolism in rats treated with carbon tetrachloride

Seyhan GÜMÜŞLÜ, Suna ÖMEROĞLU, Seda DEVAY DUYGULU, Mustafa KAVUTÇU, Nilüfer BAYRAKTAR, Mine TAŞLIPINAR YAVUZ, Orhan CANBOLAT

Antinociceptive activity of some Scorzonera L. species

Hayriye Gülçin SALTAN, Özlem BAHADIR, Hanefi ÖZBEK

Evaluation of vitamin B12 level in middle-aged obese women with metabolic and nonmetabolic syndrome: Case-control study

Ali KUTLUCAN, Serkan ÖZTÜRK, İsmail KARABULUT, Gökhan CELBEK, Hayriye YILDIRIM AK, İsmail Hamdi KARA, Davut BALTACI, Ahmet ÇELER

Rating of perceived exertion in cycle ergometer: effect of maximal capacity difference

Özgür ÇAKIR KASIMAY, Ömer Utku ERZENGİN, Hızır KURTEL, Barış ÇAKIR

Evaluation of vitamin B-12 level in middle-aged obese women with metabolic and non-metabolic syndrome: case-control study

Davut BALTACI, Ali KUTLUCAN, Serkan ÖZTÜRK, İsmail KARABULUT, Hayriye AK YILDIRIM, Ahmet ÇELER, Gökhan CELBEK, İsmail Hamdi KARA

Chest radiography and computed tomography findings of cases with pandemic influenza A (H1N1/09) infection

Hasan YİĞİT, Uğur KOŞAR, Elif ERGÜN, Ali Pekcan DEMİRÖZ, Zeliha TUFAN KOÇAK, Pınar Nercis KOŞAR

Clinical and electrophysiological evaluation of shoulder functions in spinal accessory nerve-preserving neck dissection

Özgür TARKAN, Özgür SÜRMELİOĞLU, Süleyman ÖZDEMİR, Hacer BOZDEMİR, Tunay SARPEL, Ülkü TUNCER