Data Sheet 1_Timing dictates efficacy: evaluating the prophylactic and therapeutic potential of dimethyl fumarate against LPS-induced shock.pdf

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.</p>Results<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-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.</p>Conclusion<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.</p>