Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice.

ABSTRACT: We tested the anti-inflammatory agent methyl-2-acetamidoacrylate (M2AA), an ethyl pyruvate analog, in a cecal ligation-and-puncture (CLP) model of sepsis in CD-1 mice. M2AA administration at the time of CLP improved survival, renal function, kidney histology, liver injury, and splenocyte apoptosis, and lowered cytokine levels (TNF-alpha, IL-6, IFN-gamma, and IL-10). When M2AA treatment was delayed 6 h (but not 12 h), M2AA still significantly reduced kidney dysfunction, liver injury, splenocyte apoptosis, and cytokine levels. NF-kappaB, a M2AA target, was transiently activated in spleen, peaking at 6 h; kidney and liver NF-kappaB increased steadily with a plateau at 12-24 h. M2AA reduced NF-kappaB activation in spleen at 6 h and in kidney and liver at 24 h. Splenectomy diminished the abilit

SUBMITTER: Leelahavanichkul A 

PROVIDER: S-EPMC2604833 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature