Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

• DOI: 10.1371/journal.pone.0030134
• Publication Date: 2012-01-12T21:47:23Z
• Authors: Kazunori Takahashi; Hiroki Mizukami; Kosuke Kamata; Wataru Inaba; Noriaki Kato; Chihiro Hibi; Soroku Yagihashi
• Keywords: Blood urea nitrogen; Monocyte

Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury serious complication systemic and its genesis still unclear posing difficulty for an effective treatment. Aldose reductase (AR) inhibitor recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure lethality. We studied the effects AR on LPS-induced acute mechanism. Methods Mice were injected with LPS (Fidarestat 32 mg/kg) before or after injection examined mortality, severity renal pathology. Serum concentrations cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 tumor necrosis factor-α) their mRNA expressions in lung, liver, spleen measured. also evaluated polyol metabolites kidney. Results Mortality rate within 72 hours was significantly less LPS-injected mice treated both (29%) (40%) than untreated (90%). showed marked increases blood urea nitrogen, creatinine cytokines, treatment suppressed changes. associated vacuolar degeneration apoptosis tubular cells as well infiltration neutrophils macrophages. With improvement such pathological findings, elevation cytokine levels organs sorbitol accumulation. Conclusion ameliorated injury, resulting lowered mortality.