{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:32Z","timestamp":1785428072476,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["ORF-2026-554"],"award-info":[{"award-number":["ORF-2026-554"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ORF-2026-554"],"award-info":[{"award-number":["ORF-2026-554"]}],"id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Omega-6 polyunsaturated fats (\u03c9-6 PUFAs) are vital for many physiological functions, but their impact on cardiovascular disease (CVD) risk is controversial. Eryptosis alters blood viscosity by providing a procoagulant surface and leads to anemia, which is a recognized risk factor for CVD. This study examines the toxic mechanisms of adrenic acid (ADR), an \u03c9-6 PUFA enriched in inflammatory and oxidative conditions, in red blood cells (RBCs). Purified RBCs were prepared from healthy volunteers and treated with 10\u2013100 \u03bcM of ADR for 24 h at 37 \u00b0C under various physiological conditions. Eryptotic markers were studied through flow cytometry including Ca2+ (Fluo4\/AM), loss of volume (forward scatter), phosphatidylserine (PS) exposure (annexin-V-FITC), and oxidative stress (H2DCFDA). Moreover, hemolytic markers were measured by colorimetric methods, whereas cellular morphology was visualized using a scanning electron microscope. ADR led to significant Ca2+ elevation, cell shrinkage and schistocyte formation, PS externalization, hemolysis, and oxidative stress. While guanosine, heparin, and NSC 23766 prevented eryptosis and hemolysis, melatonin, ATP, adenine, and L-NAME only prevented eryptosis. Conversely, mannitol and urea exacerbated eryptosis, whereas caffeine, mannitol, and urea under Ca2+ deprivation and membrane potential dissipation aggravated hemolysis. ADR induces erythrocyte membrane injury and eryptosis through Ca2+ elevation, oxidative stress, and metabolic exhaustion subject to inhibition by the Rac1 GTPase\/NOS\/COX pathway. Altogether, these findings present a novel mechanistic link between lipid dysregulation and RBC dysfunction which may improve dietary strategies to prevent and manage CVD.<\/jats:p>","DOI":"10.3390\/ijms27104327","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:44:26Z","timestamp":1778658266000},"page":"4327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stimulation of Eryptosis and Hemolysis by Adrenic Acid Involves Oxidative Stress, Calcium Elevation, and Metabolic Collapse"],"prefix":"10.3390","volume":"27","author":[{"given":"Feryal H.","family":"Alharthy","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawaher","family":"Alsughayyir","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-9154","authenticated-orcid":false,"given":"Mohammad A.","family":"Alfhili","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1161\/HYPERTENSIONAHA.109.144147","article-title":"Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors","volume":"55","author":"Kopf","year":"2010","journal-title":"Hypertension"},{"key":"ref_2","first-page":"466","article-title":"Omega-6 fatty acids and the risk of cardiovascular disease: Insights from a systematic review and meta-analysis of randomized controlled trials and a Mendelian randomization study","volume":"18","author":"Mazidi","year":"2022","journal-title":"Arch. 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