{
  "abstract": "Background: 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.\n\nAim: to study DMF’s effect on endotoxemia-induced AKI in a mouse in vivo model.\n\nMethods: We divided the mice (Swiss albino) into eight equal groups. The endotoxemia-induced AKI was treated by intraperitoneal injection with LPS (5 mg/kg). Prophylactic cohorts received oral DMF (50 or 100 mg/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.\n\nResults: 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-κB inflammatory pathway and the overall renal cytoarchitecture was preserved. On the other hand, therapeutic DMF demonstrated a unique anti-inflammatory “ceiling effect” where both low and high doses inhibited NF-κB 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.\n\nConclusion: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Toxicology, College of Pharmacy, Al-Mustafa University , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ahmed Mohammed Mahmood"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mfjszk0r1r4b.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1966178",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669161/?tool=EBI",
  "id": "4mfjszk0r1r4b",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13669161",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7215083386",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669161/pdf/?tool=EBI",
  "pmcid": "PMC13669161",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4mfjszk0r1r4b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13669161",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13669161"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1966178",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1966178/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Timing dictates efficacy: evaluating the prophylactic and therapeutic potential of dimethyl fumarate against LPS-induced shock",
  "title_text": "Timing dictates efficacy: evaluating the prophylactic and therapeutic potential of dimethyl fumarate against LPS-induced shock",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/4mfjszk0r1r4b",
  "venue": "Frontiers in pharmacology",
  "versions": []
}