N-acetylcysteine increases total glutathione levels in experimental models of heart diseases: a systematic review and meta-analysis

N-acetylcysteine increases total glutathione levels in experimental models of heart diseases: a systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review N-acetylcysteine increases total glutathione levels in experimental models of heart diseases: a systematic review and meta-analysis Aimée Souto Ferreira, Thomas Schaan, Luis E. Rohde, Michael Andrades This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5238928/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Cardiovascular diseases (CVD) are the leading cause of death globally. Oxidative stress plays a significant role in cell damage, inflammation, and progression of CVD. The use of N-acetylcysteine (NAC), a well-known antioxidant and a precursor to glutathione (GSH), has shown potential in preventing different types of CVD. Yet, there is limited data assessing NAC’s impact on GSH levels in animal models of CVD. Objective : To evaluate reduced glutathione (GSH) and total glutathione levels in cardiac tissue or serum/plasma from animals with established heart disease treated with NAC. Method: The literature search included PubMed, Embase, WoS, Scielo, Lilacs/BINACIS, and rXiv databases. The search in the databases was completed in December 2022. Results : We identified 619 articles, fully reviewed 35, and included 7 in the meta-analysis. The included studies varied in cardiovascular disease models, NAC doses, and outcomes. Meta-analysis revealed that NAC supplementation significantly increased total glutathione levels (SMD = 1.23, 95% CI = 0.56–1.89; p = 0.0003) with low heterogeneity ( I² = 37%). GSH levels showed a marginal increase (SMD = 2.49, 95% CI = -0.20–5.18; p = 0.07), with high heterogeneity ( I² = 93%). Conclusion : NAC supplementation effectively increases total glutathione in animal models of heart disease. The impact on GSH levels was less clear, possibly due to dose variability and limited study numbers. Standardization of NAC dosing and improved methodological reporting are needed for more consistent and clinically relevant findings. Cardiac & Cardiovascular Systems General Biochemistry Translational Medicine cardiovascular disease oxidative stress animal model antioxidant Full Text Additional Declarations The authors declare no competing interests. Supplementary Files FerreiraAS2024OnlineResource1.xlsx Online Resource 1 FerreiraAS2024OnlineResource2.xlsx Online Resource 2 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5238928","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":364519069,"identity":"ba84a623-7cae-442e-80ae-74fcb6190cd7","order_by":0,"name":"Aimée Souto Ferreira","email":"","orcid":"https://orcid.org/0000-0001-8874-9048","institution":"Hospital de Clínicas de Porto Alegre","correspondingAuthor":false,"prefix":"","firstName":"Aimée","middleName":"Souto","lastName":"Ferreira","suffix":""},{"id":364519070,"identity":"a9ee8c97-b8d5-4b74-90c4-e04e5b8f8ba4","order_by":1,"name":"Thomas Schaan","email":"","orcid":"","institution":"Hospital de Clínicas de Porto Alegre","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Schaan","suffix":""},{"id":364519071,"identity":"6c471383-2ece-4dc7-93df-9e08ebc481b2","order_by":2,"name":"Luis E. 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Oxidative stress plays a significant role in cell damage, inflammation, and progression of CVD. The use of N-acetylcysteine (NAC), a well-known antioxidant and a precursor to glutathione (GSH), has shown potential in preventing different types of CVD. Yet, there is limited data assessing NAC’s impact on GSH levels in animal models of CVD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To evaluate reduced glutathione (GSH) and total glutathione levels in cardiac tissue or serum/plasma from animals with established heart disease treated with NAC. Method: The literature search included PubMed, Embase, WoS, Scielo, Lilacs/BINACIS, and rXiv databases. The search in the databases was completed in December 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: We identified 619 articles, fully reviewed 35, and included 7 in the meta-analysis. The included studies varied in cardiovascular disease models, NAC doses, and outcomes. Meta-analysis revealed that NAC supplementation significantly increased total glutathione levels (SMD = 1.23, 95% CI = 0.56–1.89; p = 0.0003) with low heterogeneity (\u003cem\u003eI²\u003c/em\u003e = 37%). GSH levels showed a marginal increase (SMD = 2.49, 95% CI = -0.20–5.18; p = 0.07), with high heterogeneity (\u003cem\u003eI²\u003c/em\u003e = 93%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: NAC supplementation effectively increases total glutathione in animal models of heart disease. The impact on GSH levels was less clear, possibly due to dose variability and limited study numbers. 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