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The Effect of Post-Treatment N-Acetylcysteine in LPS-Induced Acute Lung Injury of Rats

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2012, v.73 no.1, pp.22-31
https://doi.org/10.4046/trd.2012.73.1.22










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Abstract

Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)were measured in BALF. Nuclear factor κB (NF-κB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-α and IL-1β concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5±2.8 nmol/mL vs. 16.5±1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4±1.8 unit/g vs. 11.2±6.3 unit/g, tissue) (p<0.048). The concentration of NF-κB in NAC treatment group was significantly lower than that of LPS group (0.3±0.1 ng/μL vs. 0.4±0.2 ng/μL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-κB activation.

keywords
Acetylcysteine, Acute Lung Injury, Antioxidants

Reference

1.

1. Costa EL, Schettino IA, Schettino GP. The lung in sepsis: guilty or innocent? Endocr Metab Immune Disord Drug Targets 2006;6:213-6.

2.

2. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 2004;202:145-56.

3.

3. Koh Y, Lee YM, Lim CM, Lee SS, Shim TS, Lee SD, et al. Effects of heat pretreatment on histopathology, cytokine production, and surfactant in endotoxin-induced acute lung injury. Inflammation 2001;25:187-96.

4.

4. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-76.

5.

5. Zhang H, Slutsky AS, Vincent JL. Oxygen free radicals in ARDS, septic shock and organ dysfunction. Intensive Care Med 2000;26:474-6.

6.

6. Chow CW, Herrera Abreu MT, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 2003;29:427-31.

7.

7. Metnitz PG, Bartens C, Fischer M, Fridrich P, Steltzer H, Druml W. Antioxidant status in patients with acute respiratory distress syndrome. Intensive Care Med 1999;25:180-5.

8.

8. Ferruzza S, Scarino ML, Gambling L, Natella F, Sambuy Y. Biphasic effect of iron on human intestinal Caco-2 cells: early effect on tight junction permeability with delayed onset of oxidative cytotoxic damage. Cell Mol Biol (Noisy-le-grand) 2003;49:89-99.

9.

9. Wheeler AP, Bernard GR. Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet 2007;369:1553-64.

10.

10. Dana R, Malech HL, Levy R. The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils. Biochem J 1994;297(Pt 1):217-23.

11.

11. Atkinson MC. The use of N-acetylcysteine in intensive care. Crit Care Resusc 2002;4:21-7.

12.

12. Jepsen S, Herlevsen P, Knudsen P, Bud MI, Klausen NO. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Crit Care Med 1992;20:918-23.

13.

13. Bernard GR, Wheeler AP, Arons MM, Morris PE, Paz HL, Russell JA, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest 1997;112:164-72.

14.

14. Muzykantov VR. Targeting of superoxide dismutase and catalase to vascular endothelium. J Control Release 2001;71:1-21.

15.

15. Christofidou-Solomidou M, Muzykantov VR. Antioxidant strategies in respiratory medicine. Treat Respir Med 2006;5:47-78.

16.

16. Kao SJ, Wang D, Lin HI, Chen HI. N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clin Exp Pharmacol Physiol 2006;33:33-40.

17.

17. Mitsopoulos P, Omri A, Alipour M, Vermeulen N, Smith MG, Suntres ZE. Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents. Int J Pharm 2008;363:106-11.

18.

18. Kim BY, Lee YM. Moxifloxacin ameliorates oleic acidinduced acute lung injury by modulation of neutrophilic oxidative stress in rats. Tuberc Respir Dis 2010;68:334-44.

19.

19. Brown RE, Jarvis KL, Hyland KJ. Protein measurement using bicinchoninic acid: elimination of interfering substances. Anal Biochem 1989;180:136-9.

20.

20. Thakur V, Pritchard MT, McMullen MR, Wang Q, Nagy LE. Chronic ethanol feeding increases activation of NADPH oxidase by lipopolysaccharide in rat Kupffer cells: role of increased reactive oxygen in LPS-stimulated ERK1/2 activation and TNF-alpha production. J Leukoc Biol 2006;79:1348-56.

21.

21. Lima Trajano ET, Sternberg C, Caetano M, Santos Silva MA, Porto LC, Santos JC, et al. Endotoxin-induced acute lung injury is dependent upon oxidative response. Inhal Toxicol 2011;23:918-26.

22.

22. Kim JH, Yoon DW, Jung KH, Kim HO, Ha ES, Lee KJ, et al. The effects of nuclear factor-kappa B decoy oligodeoxynucleotide on lipopolysaccharide-induced direct acute lung injury. Tuberc Respir Dis 2009;67:95- 104.

23.

23. Yoshida M, Yoshimura N, Hangai M, Tanihara H, Honda Y. Interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor gene expression in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 1994;35:1107- 13.

24.

24. Menezes SL, Bozza PT, Neto HC, Laranjeira AP, Negri EM, Capelozzi VL, et al. Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol 2005;98:1777-83.

25.

25. Macdonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth 2003;90: 221-32.

26.

26. Cadenas S, Cadenas AM. Fighting the stranger-antioxidant protection against endotoxin toxicity. Toxicology 2002;180:45-63.

27.

27. Liu SF, Ye X, Malik AB. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes. Circulation 1999; 100:1330-7.

28.

28. Pelosi P, D'Onofrio D, Chiumello D, Paolo S, Chiara G, Capelozzi VL, et al. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J Suppl 2003;42:48s-56s.

29.

29. Matsuda N, Hattori Y, Jesmin S, Gando S. Nuclear factor- kappaB decoy oligodeoxynucleotides prevent acute lung injury in mice with cecal ligation and puncture-induced sepsis. Mol Pharmacol 2005;67:1018-25.

30.

30. Matsuda N, Hattori Y, Takahashi Y, Nishihira J, Jesmin S, Kobayashi M, et al. Therapeutic effect of in vivo transfection of transcription factor decoy to NF-kappaB on septic lung in mice. Am J Physiol Lung Cell Mol Physiol 2004;287:L1248-55.

31.

31. Tasaka S, Amaya F, Hashimoto S, Ishizaka A. Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome. Antioxid Redox Signal 2008;10:739-53.

32.

32. Rahman I. Antioxidant therapies in COPD. Int J Chron Obstruct Pulmon Dis 2006;1:15-29.

33.

33. Victor VM, Rocha M, De la Fuente M. Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 2004;4:327-47.

34.

34. Sadowska AM, Manuel-Y-Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther 2007;20: 9-22.

35.

35. Vassilev D, Hauser B, Bracht H, Iványi Z, Schoaff M, Asfar P, et al. Systemic, pulmonary, and hepatosplanchnic effects of N-acetylcysteine during long-term porcine endotoxemia. Crit Care Med 2004;32:525-32.

Tuberculosis & Respiratory Diseases