{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:44Z","timestamp":1790834444219,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute kidney injury (AKI) is a serious and often fatal condition that is caused by endotoxemia as a result of systemic inflammation and uncontrolled oxidative stress. Although dimethyl fumarate (DMF) has shown to have immunomodulatory and antioxidant activity, its specific prophylactic and therapeutic activity in endotoxemia-induced AKI remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      to study DMF\u2019s effect on endotoxemia-induced AKI in a mouse\n                      <jats:italic>in vivo<\/jats:italic>\n                      model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We divided the mice (Swiss albino) into eight equal groups. The endotoxemia-induced AKI was treated by intraperitoneal injection with LPS (5\u00a0mg\/kg). Prophylactic cohorts received oral DMF (50 or 100\u00a0mg\/kg\/day) for three consecutive days prior to the challenge. Therapeutic cohorts were given a single DMF dose one hour after the treatment. At six hours, gross renal function (BUN, creatinine), cytokine levels, Nrf2\/HO-1 activation, oxidative damage biomarkers, inflammasome\/apoptotic pathways and acute tubular necrosis (ATN) histopathology were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LPS challenge resulted in severe renal dysfunction, the onset of a massive cytokine storm and acute tubular destruction. The pre-treatment of DMF prevented the TLR4\/NF-\u03baB inflammatory pathway and the overall renal cytoarchitecture was preserved. On the other hand, therapeutic DMF demonstrated a unique anti-inflammatory \u201cceiling effect\u201d where both low and high doses inhibited NF-\u03baB activation. Therapeutic DMF was more robust in structural and functional rescue, upregulating the Nrf2\/HO-1 defense axis, neutralizing reactive oxygen species, and blocking the final inflammasome priming and pyroptotic actions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The timing of intervention fundamentally dictates pharmacological efficacy. Prophylaxis offers strong preventative shielding, whereas high-dose therapeutic DMF successfully mitigates ongoing oxidative storms, providing a compelling and highly translatable rationale for clinical repurposing in critical care nephrology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1966178","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:47Z","timestamp":1790833307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing dictates efficacy: evaluating the prophylactic and therapeutic potential of dimethyl fumarate against LPS-induced shock"],"prefix":"10.3389","volume":"17","author":[{"given":"Ahmed Mohammed","family":"Mahmood","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Al-Mustafa University","place":["Baghdad, Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3389\/fimmu.2016.00278","article-title":"Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases","volume":"7","author":"Al-Jaderi","year":"2016","journal-title":"Front. 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