Evaluation of the efficacy of N-Acetylcysteine combined with standard quadruple therapy versus standard quadruple therapy alone for Helicobacter pylori eradication
DOI:
https://doi.org/10.61882/jcbior.4.4.287Keywords:
Helicobacter pylori, N-acetyl cysteine, Proton pump inhibitorAbstract
N-acetyl cysteine (NAC) has recently been proposed as an adjunctive therapy for the eradication of Helicobacter pylori infection due to its mucolytic, antioxidant, and antimicrobial properties. This study aimed to evaluate the efficacy of adding NAC to the standard 4-drug regimen consisting of amoxicillin, clarithromycin, pantoprazole, and bismuth subcitrate. In this double-blind, randomized clinical trial, 92 patients with confirmed H. pylori infection were randomly assigned to either the intervention group or the control group (46 patients each) using a randomized block design. All patients received a 14-day course of amoxicillin, clarithromycin, pantoprazole, and bismuth subcitrate. The intervention group also received NAC tablets, while the control group received a placebo, matched in dose and schedule. Eradication of H. pylori was assessed two weeks after treatment cessation using the urea breath test. H. pylori eradication was achieved in 78.3% of patients in the intervention group (95% CI: 66.38–90.21) and 71.7% in the placebo group (95% CI: 59.57–84.49), with no statistically significant difference between groups (p=0.804). The overall eradication rate among all participants was 75% (95% CI: 64.72–85.77). Of the 23 patients who failed treatment, 14 were smokers, and smoking was significantly associated with treatment failure (p<0.0001). Notably, eradication rates among smokers were significantly higher in the NAC group compared to the placebo group (p=0.041). The addition of NAC to standard quadruple therapy did not significantly improve H. pylori eradication overall, but its potential benefit in specific subgroups such as smokers suggests the need for further research.
References
1. Graham DY, Lee SY. How to effectively use bismuth quadruple therapy: the good, the bad, and the ugly. Gastroenterology Clinics of North America. 2015;44(3):537. DOI: 10.1016/j.gtc.2015.05.003 PMID: 26314667
2. Vieira RR, Fontes LE, Pacheco RL, Fernandes MA, Malta PP, Riera R. Proton pump inhibitor‐and clarithromycin‐based triple therapies for Helicobacter pylori eradication. The Cochrane Database of Systematic Reviews. 2020;2020(9):CD013734. DOI: 10.1002/14651858.CD013734
3. Gupta N, Kumar A, Verma VK. Strategies adopted by gastric pathogen Helicobacter pylori for a mature biofilm formation: Antimicrobial peptides as a visionary treatment. Microbiological Research. 2023;273:127417. DOI: 10.1016/j.micres.2023.127417
4. Sharndama HC, Mba IE. Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms. Brazilian Journal of Microbiology. 2022;53(1):33-50. DOI: 10.1007/s42770-021-00675-0
5. Kao CY, Sheu BS, Wu JJ. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis. Biomedical journal. 2016;39(1):14-23. DOI: 10.1016/j.bj.2015.06.002
6. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological reviews. 2014;94(2):329-54. DOI: 10.1152/physrev.00040.2012 PMID: 24692350
7. Zhang S, Shen Y, Liu H, Zhu D, Fang J, Pan H, Liu W. Inflammatory microenvironment in gastric premalignant lesions: implication and application. Front Immunol. 2023;14:1297101. DOI: 10.3389/fimmu.2023.1297101 PMID: 38035066
8. Sah DK, Arjunan A, Lee B, Jung YD. Reactive Oxygen Species and H. pylori Infection: A Comprehensive Review of Their Roles in Gastric Cancer Development. Antioxidants (Basel). 2023;12(9):1712. DOI: 10.3390/antiox12091712 PMID: 37760015
9. Tieu S, Charchoglyan A, Paulsen L, Wagter-Lesperance LC, Shandilya UK, Bridle BW, Mallard BA, Karrow NA. N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants (Basel). 2023;12(10):1867. DOI: 10.3390/antiox12101867 PMID: 37891946
10. Schwalfenberg GK. N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). J Nutr Metab. 2021;2021:9949453. DOI: 10.1155/2021/9949453. PMID: 34221501
11. Meziu E, Shehu K, Koch M, Schneider M, Kraegeloh A. Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity. International Journal of Pharmaceutics: X. 2023;6:100212. DOI: 10.1016/j.ijpx.2023.100212
12. Dascălu RI, Bolocan A, Păduaru DN, Constantinescu A, Mitache MM, Stoica AD, Andronic O. Multidrug resistance in Helicobacter pylori infection. Frontiers in Microbiology. 2023;14:1128497. DOI:10.3389/fmicb.2023.1128497
13. White B, Winte M, DeSipio J, Phadtare S. Clinical factors implicated in antibiotic resistance in Helicobacter pylori patients. Microorganisms. 202;10(2):322. DOI: 10.3390/microorganisms10020322
14. Cardos IA, Zaha DC, Sindhu RK, Cavalu S. Revisiting therapeutic strategies for H. pylori treatment in the context of antibiotic resistance: focus on alternative and complementary therapies. Molecules. 2021;26(19):6078. DOI: 10.3390/molecules26196078
15. Karbasi A, Hosseini H, Shohrati M, Amini M, Najafian B. Effect of oral N-acetyl cysteine on eradication of Helicobacter pylori in patients with dyspepsia. Minerva Gastroenterologica e Dietologica. 2013;59(1):107-12. PMID: 23478248
16. Yoon H, Lee DH, Jang ES, Kim J, Shin CM, Park YS, Hwang JH, Kim JW, Jeong SH, Kim N. Effects of N-acetylcysteine on first-line sequential therapy for Helicobacter pylori infection: a randomized controlled pilot trial. Gut and liver. 2015;10(4):520. DOI: 10.5009/gnl15048 PMID: 26347514
17. Emami MH, Zobeiri M, Rahimi H, Arjomandi F, Daghagzadeh H, Adibi P, Hashemi J. N-acetyl cysteine as an adjunct to standard anti-Helicobacter pylori eradication regimen in patients with dyspepsia: A prospective randomized, open-label trial. Advanced Biomedical Research. 2014;3(1):189. DOI: 10.4103/2277-9175.140403 PMID: 25298958
18. Hamidian SM, Aletaha NS, Taslimi R, Montazeri M. An Additive Effect of Oral N-Acetyl Cysteine on Eradication of Helicobacter pylori. J Pathog. 2015;2015:540271. DOI: 10.1155/2015/540271 PMID: 26421191
19. Fontes LES, Martimbianco ALC, Zanin C, Riera R. N-acetylcysteine as an adjuvant therapy for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2019 ;2(2):CD012357. DOI: 10.1002/14651858.CD012357.pub2 PMID: 30746681
20. Han L, Shu X, Wang J. Helicobacter pylori-mediated oxidative stress and gastric diseases: a review. Frontiers in microbiology. 2022;13:811258. DOI: 10.3389/fmicb.2022.811258
21. Butcher LD, den Hartog G, Ernst PB, Crowe SE. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric Carcinogenesis. Cell Mol Gastroenterol Hepatol. 2017;3(3):316-322. DOI: 10.1016/j.jcmgh.2017.02.002 PMID: 28462373
22. Pedre B, Barayeu U, Ezeriņa D, Dick TP. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacology & therapeutics. 2021;228:107916. DOI: 10.1016/j.pharmthera.2021.107916
23. Tenório MCDS, Graciliano NG, Moura FA, Oliveira ACM, Goulart MOF. N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel). 2021;10(6):967. DOI: 10.3390/antiox10060967 PMID: 34208683
24. Miyazaki K, Sasaki A, Mizuuchi H. Advances in the Evaluation of Gastrointestinal Absorption Considering the Mucus Layer. Pharmaceutics. 2023 Nov 30;15(12):2714. DOI: 10.3390/pharmaceutics15122714 PMID: 38140055
25. Gupta A, Shetty S, Mutalik S, Chandrashekar H R, K N, Mathew EM, Jha A, Mishra B, Rajpurohit S, Ravi G, Saha M, Moorkoth S. Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon. 2023;9(10):e20406. DOI: 10.1016/j.heliyon.2023.e20406 PMID: 37810864
26. Navabi N, Johansson ME, Raghavan S, Lindén SK. Helicobacter pylori infection impairs the mucin production rate and turnover in the murine gastric mucosa. Infect Immun. 2013;81(3):829-37. DOI: 10.1128/IAI.01000-12 PMID: 23275091
27. Yoon H, Lee DH. Mucolytics as Adjuvant Agent to Improve Helicobacter pylori Eradication Rate: Still Long and Winding Road to Positive Results. Gut Liver. 2015;9(3):257-8. DOI: 10.5009/gnl15117 PMID: 25918255
28. Yu J, Yang P, Qin X, Li C, Lv Y, Wang X. Impact of smoking on the eradication of Helicobacter pylori. Helicobacter. 2022;27(1):e12860. DOI: 10.1111/hel.12860 PMID: 34708484
29. Berkowitz L, Schultz BM, Salazar GA, Pardo-Roa C, Sebastián VP, Álvarez-Lobos MM, Bueno SM. Impact of Cigarette Smoking on the Gastrointestinal Tract Inflammation: Opposing Effects in Crohn's Disease and Ulcerative Colitis. Front Immunol. 2018;9:74. DOI: 10.3389/fimmu.2018.00074 PMID: 29441064
30. Ahmadkhaniha R, Yousefian F, Rastkari N. Impact of smoking on oxidant/antioxidant status and oxidative stress index levels in serum of the university students. J Environ Health Sci Eng. 2021;19(1):1043-1046. DOI: 10.1007/s40201-021-00669-y PMID: 34150292
31. Seo YS, Park JM, Kim JH, Lee MY. Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants (Basel). 2023;12(9):1732. DOI: 10.3390/antiox12091732 PMID: 37760035
32. Kamceva G, Arsova-Sarafinovska Z, Ruskovska T, Zdravkovska M, Kamceva-Panova L, Stikova E. Cigarette Smoking and Oxidative Stress in Patients with Coronary Artery Disease. Open Access Maced J Med Sci. 2016;4(4):636-640. DOI: 10.3889/oamjms.2016.117 PMID: 28028404
33. Gurbuz AK, Ozel AM, Ozturk R, Yildirim S, Yazgan Y, Demirturk L. Effect of N-acetyl cysteine on Helicobacter pylori. South Med J. 2005;98(11):1095-7. DOI: 10.1097/01.smj.0000182486.39913.da PMID: 16351030
Downloads
Published
Issue
Section
License
Copyright (c) 2023 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
