Protective effect of S-nitrosoglutathione pretreatment on acute lung injury in septic rats

Document Type: Original Article

Authors

1 Department of Respiratory and Critical Care, Ningbo First Hospital Longshan Hospital Medical and Health Group, Ningbo, Zhejiang Province, P.R China

2 Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, Zhejiang Province, P.R China

Abstract

Objective(s): To investigate the protective effect of S-nitrosoglutathione (SNG) pretreatment on acute lung injury (ALI) in septic rats.
Materials and Methods: We constructed a rat model of sepsis by cecal ligation and perforation (CLP), and randomly divided into Sham, CLP, and CLP+SNG (0.25 and 0.5 mg/kg) groups. We used H&E staining and lung wet/dry ratio to assess the severity of lung injury, detected the levels of protein and cells in bronchoalveolar lavage fluid (BALF) and the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA in the lung tissue, and assessed the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in the lung tissue.
Results: A rat model of sepsis was successfully constructed by CLP, and pretreatment of SNG significantly increased the survival of septic rats (P<0.001) and decreased the lung tissue injury scores (P<0.001) and lung wet/dry ratio (P<0.01) in a dose-dependent manner. Furtherly, SNG pretreatment significantly reduced the number of total cells, total protein, neutrophils, and lympholytes (all P<0.001) in BALF, and which also decreased the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA (all P<0.001) in the lungs of CLP-induced rats. Moreover, pretreatment of SNG significantly increased the levels of anti-oxidant enzymes GSH, SOD, GSH-Px, and catalase (all P<0.001) in the lung tissue of septic rats.
Conclusion: SNG pretreatment has a protective effect on ALI in septic rats, and the specific mechanism may be related to anti-endotoxic, anti-inflammatory, and anti-oxidative properties.

Keywords


1. Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191:1147-1157.
2. Su F, Nguyen ND, Creteur J, Cai Y, Nagy N, Anh-Dung H, et al. Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury. Shock 2004; 22:145-150.
3. Wang YC, Liu QX, Zheng Q, Liu T, Xu XE, Liu XH, et al. Dihydromyricetin alleviates sepsis-induced acute lung injury through inhibiting NLRP3 inflammasome-dependent pyroptosis in mice model. Inflammation 2019; 42:1301-1310.
4. Zhang H, Sha J, Feng X, Hu X, Chen Y, Li B, et al. Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signaling pathway in rats. Int Immunopharmacol 2019; 74:105717.
5. Cinar I, Sirin B, Aydin P, Toktay E, Cadirci E, Halici I, et al. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sci 2019; 221: 327-334.
6. Melvin AC, Jones WM, Lutzke A, Allison CL, Reynolds MM. S-Nitrosoglutathione exhibits greater stability than S-nitroso-N-acetylpenicillamine under common laboratory conditions: A comparative stability study. Nitric Oxide 2019; 92:18-25.
7. Fan H, Zhao Y, Zhu JH. S-nitrosoglutathione protects lipopolysaccharide-induced acute kidney injury by inhibiting toll-like receptor 4-nuclear factor-κB signal pathway. J Pharm Pharmacol 2019; 71:1255-1261.
8. Gaston B, Reilly J, Drazen JM, Fackler J, Ramdev P, Arnelle D, et al. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA 1993; 90:10957-10961.
9. Langford EJ, Brown AS, Wainwright RJ, de Belder AJ, Thomas MR, Smith RE, et al. Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty. Lancet 1994; 344:1458-1460.
10. Ye S, Dong J, Han B. Protective effect of reduced glutathione and venous systemic oxygen persufflation on rat steatotic graft following liver transplantation. J Surg Res 2010; 158:138-146.
11. Baydas G, Gursu MF, Yilmaz S, Canpolat S, Yasar A, Cikim G, et al. Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats. Neurosci Lett 2002; 323:195-198.
12. Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Verney C, Pons B, et al. Timing of renal support and outcome of septic shock and acute respiratory distress syndrome. A Post hoc analysis of the AKIKI randomized clinical trial. Am J Respir Crit Care Med 2018;198:58-66.
13. Calfee CS, Gallagher D, Abbott J, Thompson BT, Matthay MA; NHLBI ARDS Network. Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Crit Care Med 2012; 40:1731-1737.
14. Watson RS, Asaro LA, Hertzog JH, Sorce LR, Kachmar AG, Dervan LA, et al. Long-term outcomes after protocolized sedation versus usual care in ventilated pediatric patients. Am J Respir Crit Care Med 2018; 197:1457-1467.
15. Sun C, Wu Q, Zhang X, He Q, Zhao H. Mechanistic evaluation of the protective effect of carnosine on acute lung injury in sepsis rats. Pharmacology 2017; 100:292-300.
16. Zhang Y, Yu W, Han D, Meng J, Wang H, Cao G. L-lysine ameliorates sepsis-induced acute lung injury in a lipopolysaccharide-induced mouse model. Biomed Pharmacother 2019; 118: 109307.
17. Turan I, Sayan Ozacmak H, Ozacmak VH, Barut F, Ozacmak ID. The effects of S-nitrosoglutathione on intestinal ischemia reperfusion injury and acute lung injury in rats: Roles of oxidative stress and NF-κB. Tissue Cell 2018; 52:35-41.
18. Menden H, Xia S, Mabry SM, Noel-MacDonnell J, Rajasingh J, Ye SQ, et al. Histone deacetylase 6 regulates endothelial MyD88-dependent canonical TLR signaling, lung inflammation, and alveolar remodeling in the developing lung. Am J Physiol Lung Cell Mol Physiol 2019; 317:L332-L346.
19. Chen X, Wang T, Song L, Liu X. Activation of multiple Toll-like receptors serves different roles in sepsis-induced acute lung injury. Exp Ther Med 2019; 18:443-450.
20. Hu X, Liu S, Zhu J, Ni H. Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF-κB signaling pathway and in vitro. J Cell Biochem 2019; 120:8956-8964.
21. Qian M, Lou Y, Wang Y, Zhang M, Jiang Q, Mo Y, et al. PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT. Free Radic Biol Med 2018; 118:23-34.
22. Jingyan L, Yujuan G, Yiming Y, Lingpeng Z, Tianhua Y, Mingxing M. Salidroside Attenuates LPS-Induced Acute Lung Injury in Rats. Inflammation 2017; 40:1520-1531.
23. Zhang HX, Duan GL, Wang CN, Zhang YQ, Zhu XY, Liu YJ. Protective effect of resveratrol against endotoxemia-induced lung injury involves the reduction of oxidative/nitrative stress. Pulm Pharmacol Ther 2014; 27:150-155.