Influence of Dose and Exposition Time in the Effectiveness of -Acetyl-l-cysteine Treatment in A549 Human Epithelial Cells

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 May 5

PMID 37144195

Authors

Paula Montero

Ines Roger

Cristina Estornut

Javier Milara

Julio Cortijo

Affiliations

Soon will be listed here.

Abstract

-Acetyl-l-cysteine (NAC) acts as a precursor of the tripeptide glutathione (GSH), one of the principal cell mechanisms for reactive oxygen species (ROS) detoxification. Chronic obstructive pulmonary disease (COPD) is associated with enhanced inflammatory response and oxidative stress and NAC has been used to suppress various pathogenic processes in this disease. Studies show that the effects of NAC are dose-dependent, and it appears that the efficient doses are usually higher than the achieved plasma concentrations. However, to date, the inconsistencies between the NAC antioxidant and anti-inflammatory effects, by reproducing the NAC plasma concentrations as well as high NAC concentrations. To do so, A549 were transfected with polyinosinic-polycytidylic acid (Poly (I:C)) and treated with NAC at different treatment periods. Oxidative stress, release of proinflammatory mediators and NFkB activation were analyzed. Results suggest that NAC at low doses in chronic administration has sustained antioxidant and anti-inflammatory effects, while acute treatment with high dose NAC exerts a strong antioxidant and anti-inflammatory response.

Citing Articles

The Influence of N-Acetylcysteine-Enriched Hydrogels on Wound Healing in a Murine Model of Type II Diabetes Mellitus.

Stachura A, Sobczak M, Kedra K, Kopka M, Kopka K, Wlodarski P Int J Mol Sci. 2024; 25(18).

PMID: 39337474 PMC: 11432576. DOI: 10.3390/ijms25189986.

Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective.

Santus P, Signorello J, Danzo F, Lazzaroni G, Saad M, Radovanovic D J Clin Med. 2024; 13(14).

PMID: 39064168 PMC: 11278452. DOI: 10.3390/jcm13144127.

Molecular Mechanisms of N-Acetylcysteine in RSV Infections and Air Pollution-Induced Alterations: A Scoping Review.

Wrotek A, Badyda A, Jackowska T Int J Mol Sci. 2024; 25(11).

PMID: 38892239 PMC: 11172664. DOI: 10.3390/ijms25116051.

References

Cazzola M, Calzetta L, Facciolo F, Rogliani P, Matera M . Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation. Respir Res. 2017; 18(1):26. PMC: 5260037. DOI: 10.1186/s12931-016-0500-y. View

Aizawa H, Koarai A, Shishikura Y, Yanagisawa S, Yamaya M, Sugiura H . Oxidative stress enhances the expression of IL-33 in human airway epithelial cells. Respir Res. 2018; 19(1):52. PMC: 5872512. DOI: 10.1186/s12931-018-0752-9. View

Oka S, Kamata H, Kamata K, Yagisawa H, Hirata H . N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases. FEBS Lett. 2000; 472(2-3):196-202. DOI: 10.1016/s0014-5793(00)01464-2. View

Desaki M, Takizawa H, Kasama T, Kobayashi K, Morita Y, Yamamoto K . Nuclear factor-kappa b activation in silica-induced interleukin 8 production by human bronchial epithelial cells. Cytokine. 2000; 12(8):1257-60. DOI: 10.1006/cyto.2000.0704. View

Cazzola M, Calzetta L, Page C, Jardim J, Chuchalin A, Rogliani P . Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015; 24(137):451-61. PMC: 9487680. DOI: 10.1183/16000617.00002215. View

Zafarullah M, Li W, Sylvester J, Ahmad M . Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 2003; 60(1):6-20. PMC: 11138873. DOI: 10.1007/s000180300001. View

Messier E, Day B, Bahmed K, Kleeberger S, Tuder R, Bowler R . N-acetylcysteine protects murine alveolar type II cells from cigarette smoke injury in a nuclear erythroid 2-related factor-2-independent manner. Am J Respir Cell Mol Biol. 2013; 48(5):559-67. PMC: 3707381. DOI: 10.1165/rcmb.2012-0295OC. View

Sadowska A, Manuel-Y-Keenoy B, De Backer W . 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. 2006; 20(1):9-22. DOI: 10.1016/j.pupt.2005.12.007. View

Rushworth G, Megson I . Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2013; 141(2):150-9. DOI: 10.1016/j.pharmthera.2013.09.006. View

10.

Zhang J, Zhang J, Fang L, Liu L, Fu W, Dai L . Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter. Drug Des Devel Ther. 2015; 9:6379-87. PMC: 4676509. DOI: 10.2147/DDDT.S91823. View

11.

Chikahisa L, Oyama Y, Okazaki E, Noda K . Fluorescent estimation of H2O2-induced changes in cell viability and cellular nonprotein thiol level of dissociated rat thymocytes. Jpn J Pharmacol. 1996; 71(4):299-305. DOI: 10.1254/jjp.71.299. View

12.

Papi A, Luppi F, Franco F, Fabbri L . Pathophysiology of exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006; 3(3):245-51. DOI: 10.1513/pats.200512-125SF. View

13.

Zheng J, Wen F, Bai C, Wan H, Kang J, Chen P . Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014; 2(3):187-94. DOI: 10.1016/S2213-2600(13)70286-8. View

14.

Calzetta L, Matera M, Rogliani P, Cazzola M . Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2018; 12(8):693-708. DOI: 10.1080/17476348.2018.1495562. View

15.

Matera M, Calzetta L, Cazzola M . Oxidation pathway and exacerbations in COPD: the role of NAC. Expert Rev Respir Med. 2015; 10(1):89-97. DOI: 10.1586/17476348.2016.1121105. View

16.

Tse H, Raiteri L, Wong K, Yee K, Ng L, Wai K . High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest. 2013; 144(1):106-118. DOI: 10.1378/chest.12-2357. View

17.

Vaughan A, Stevanovic S, Jafari M, Rahman M, Bowman R, Fong K . The effect of diesel emission exposure on primary human bronchial epithelial cells from a COPD cohort: N-acetylcysteine as a potential protective intervention. Environ Res. 2018; 170:194-202. DOI: 10.1016/j.envres.2018.12.035. View

18.

Kirkham P, Barnes P . Oxidative stress in COPD. Chest. 2013; 144(1):266-273. DOI: 10.1378/chest.12-2664. View

19.

Zhou J, Terluk M, Basso L, Mishra U, Orchard P, Cloyd J . N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity. Biomedicines. 2020; 8(8). PMC: 7460204. DOI: 10.3390/biomedicines8080240. View

20.

Rahman I, MacNee W . Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J. 2000; 16(3):534-54. DOI: 10.1034/j.1399-3003.2000.016003534.x. View