{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:45:50Z","timestamp":1782701150494,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The pathogenesis of STEC-HUS is primarily driven by Shiga toxins (Stx), which induce endothelial injury, inflammation, platelet activation, and microvascular thrombosis. Hemolysis associated with thrombotic microangiopathy leads to the release of hemoglobin and free heme into the circulation. Free heme, an iron-containing molecule with potent pro-oxidative, pro-inflammatory, and cytotoxic properties, contributes to oxidative stress, endothelial dysfunction, complement activation, and further tissue injury. Oxidative stress plays a crucial role in both host and bacterial cells, influencing disease progression and the expression of bacterial virulence factors, including Shiga toxin. N-acetyl-L-cysteine (NAC), a precursor of glutathione (GSH) and a well-established antioxidant, has attracted attention as a potential adjunctive therapeutic agent due to its antioxidant, anti-inflammatory, antiplatelet, and cytoprotective properties. In addition, NAC may influence iron- and heme-mediated oxidative damage and improve erythrocyte resistance to oxidative stress. This review summarizes current knowledge regarding the roles of oxidative stress and free heme in STEC-HUS and examines the mechanistic rationale and current evidence supporting NAC as a potential adjunctive strategy. The available evidence remains largely indirect and preclinical; therefore, the potential role of NAC in STEC-HUS should be considered hypothesis-generating and requires further investigation in clinical studies.<\/jats:p>","DOI":"10.3390\/molecules31132264","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N-Acetyl-L-Cysteine as a Potential Adjunctive Strategy in STEC-HUS: Mechanistic Rationale and Current Evidence"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-8296","authenticated-orcid":false,"given":"Joanna","family":"Wr\u00f3blewska","sequence":"first","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7887-132X","authenticated-orcid":false,"given":"Marcin","family":"Wr\u00f3blewski","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-4796","authenticated-orcid":false,"given":"Alina","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 24 Kar\u0142owicza St., 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"bcr2012006896","DOI":"10.1136\/bcr-2012-006896","article-title":"Microbes without Frontiers: Severe Haemolytic-Uraemic Syndrome Due to E Coli O104:H4","volume":"2012","author":"Binks","year":"2012","journal-title":"BMJ Case Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/ndt\/gft470","article-title":"Outbreak of Escherichia coli O104:H4 Haemolytic Uraemic Syndrome in France: Outcome with Eculizumab","volume":"29","author":"Delmas","year":"2014","journal-title":"Nephrol. 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