Protective effect of N-acetylcysteine on acute lung injury in septic rats by inhibiting inflammation, oxidation, and apoptosis

Document Type : Original Article

Authors

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

Abstract

Objective(s): Acute lung injury (ALI) is a common comorbidity in patients with sepsis, and finding drugs that can effectively reduce its mortality is a hot spot in current research. The purpose of this study is to explore the protective mechanism of N-acetylcysteine (NAC) on ALI in septic rats.
Materials and Methods: We used NAC to intervene in septic rats to evaluate the plasma inflammatory factors and lung tissue pathological damage. Biochemical methods were used to determine the levels of oxidases in lung tissue, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) proteins, and observed lung tissue cell apoptosis.
Results: NAC pretreatment decreased the mortality of septic rats, improved lung tissue pathological damage, reduced the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, and malondialdehyde, and increased activity of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, NAC pretreatment significantly decreased iNOS protein expression and increased eNOS protein expression in lung tissue. Meanwhile, NAC significantly decreased the number of apoptosis and the levels of Bax and Caspase-3 mRNA and increased the level of Bcl-2 mRNA in the lung tissue of septic rats. 
Conclusion: NAC protects ALI in septic rats by inhibiting inflammation, oxidative stress, and apoptosis.

Keywords


1. Fan H, Zhao Y, Sun M, Zhu JH. Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, N-acetyl-β-D-glucosaminidase levels and mortality risk in septic patients with acute kidney injury. Arch Med Sci 2018;14:1381-1386.
2. Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet 2018;392(10141):75-87.
3. Esposito S, De Simone G, Boccia G, De Caro F, Pagliano P. Sepsis and septic shock: New definitions, new diagnostic and therapeutic approaches. J Glob Antimicrob Resist 2017;10:204-212.
4. Wang YM, Ji R, Chen WW, Huang SW, Zheng YJ, Yang ZT, et al. Paclitaxel alleviated sepsis-induced acute lung injury by activating MUC1 and suppressing TLR-4/NF-κB pathway. Drug Des Devel Ther 2019;13:3391-3404. 
5. Fan H, Le JW, Zhu JH. Protective Effect of N-Acetylcysteine Pretreatment on Acute Kidney Injury in Septic Rats. J Surg Res 2020;254:125-134. 
6. Song Q, Lin L, Chen L, Cheng L, Zhong W. Co-administration of N-acetylcysteine and dexmedetomidine plays a synergistic effect on protection of LPS-induced acute lung injury via correcting Th1/Th2/Th17 cytokines imbalance. Clin Exp Pharmacol Physiol 2020;47:294-301. 
7. Wang ZF, Yang YM, Fan H. Protective effect of S-nitrosoglutathione pretreatment on acute lung injury in septic rats. Iran J Basic Med Sci 2020;23:1059-1064. 
8. Park I, Kim M, Choe K, Song E, Seo H, Hwang Y, et al. Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury. Eur Respir J 2019;53:1800786.
9. Salomão R, Ferreira BL, Salomão MC, Santos SS, Azevedo LCP, Brunialti MKC. Sepsis: Evolving concepts and challenges. Braz J Med Biol Res 2019;52:e8595. 
10. Celebi D, Aydin P, Cinar I, Kutlu Z, Calik I, Halici Z, et al. Protective effect of luteolin on acute lung injury in a rat model of sepsis. Biotech Histochem 2021;96:579-585. 
11. Liu J, Du J, Cheng X, Zhang X, Li Y, Fu X, et al. Effect of Netrin-1 anti-inflammatory factor on acute lung injury in sepsis rats. Med Sci Monit 2019;25:7928-7935.
12. Chen X, Wang Y, Xie X, Chen H, Zhu Q, Ge Z, et al. Heme oxygenase-1 reduces sepsis-induced endoplasmic reticulum stress and acute lung injury. Mediators Inflamm 2018;2018:9413876. 
13. Zheng H, Liang W, He W, Huang C, Chen Q, Yi H, et al. Ghrelin attenuates sepsis-induced acute lung injury by inhibiting the NF-κB, iNOS, and Akt signaling in alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 2019;317:L381-L391. 
14. Jiang J, Huang K, Xu S, Garcia JGN, Wang C, Cai H. Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII/ERK1/2/MLCK and endothelial cell barrier dysfunction. Redox Biol 2020;36:101638.
15. Zeng M, He W, Li L, Li B, Luo L, Huang X, et al. Ghrelin attenuates sepsis-associated acute lung injury oxidative stress in rats. Inflammation 2015;38:683-690. 
16. Liu XW, Ma T, Cai Q, Wang L, Song HW, Liu Z. Elevation of serum PARK7 and IL-8 levels is associated with acute lung injury in patients with severe sepsis/septic shock. J Intensive Care Med 2019;34:662-668. 
17. Rendell R, Fairhall S, Graham S, Rutter S, Auton P, Smith A, et al. Assessment of N-acetylcysteine as a therapy for phosgene-induced acute lung injury. Toxicol Lett 2018;290:145-152.
18. Fan H, Le JW, Sun M, Zhu JH. Pretreatment with S-Nitrosoglutathione attenuates septic acute kidney injury in rats by inhibiting inflammation, oxidation, and apoptosis. Biomed Res Int 2021;2021:6678165.
19. Sun LC, Zhang HB, Gu CD, Guo SD, Li G, Lian R, et al. Protective effect of acacetin on sepsis-induced acute lung injury via its anti-inflammatory and anti-oxidative activity. Arch Pharm Res 2018;41:1199-1210.
20. Yang L, Zhang Z, Zhuo Y, Cui L, Li C, Li D, et al. Resveratrol alleviates sepsis-induced acute lung injury by suppressing inflammation and apoptosis of alveolar macrophage cells. Am J Transl Res 2018;10:1961-1975.
21. Liu W, Liu K, Zhang S, Shan L, Tang J. Tetramethylpyrazine Showed Therapeutic effects on sepsis-induced acute lung injury in rats by inhibiting endoplasmic reticulum stress protein kinase rna-like endoplasmic reticulum kinase (perk) signaling-induced apoptosis of pulmonary microvascular endothelial cells. Med Sci Monit 2018;24:1225-1231.
22. Moon SJ, Kim HY, Kim YH, Kim KS, Noh JR, Kim HJ, et al. GADD45β plays a protective role in acute lung injury by regulating apoptosis in experimental sepsis in vivo. J Cell Physiol 2018;233:7128-7138.
23. Panahi Y, Ghanei M, Hashjin MM, Rezaee R, Sahebkar A. Potential utility of N-acetylcysteine for treating mustard lung. Crit Rev Eukaryot Gene Expr 2017;27:247-266.