Approaches in Sepsis Prevention

Abstract

Background: Lipopolysaccharide (LPS) is recognized by the innate immune system via toll-like receptor 4 (TLR4) whose activation leads to the production of numerous immunoregulatory molecules and reactive oxygen species. Aim: This study was designed to investigate the effects of different interventions on LPS-induced renal oxidative and immunological changes of mice. Methods: Male Swiss mice were injected with LPS (1 mg/kg; i.p.) and pretreatment with baicalin (50 mg/kg; i.p.), parthenolide (10 mg/kg/day, i.p), SC-58125 (10 mg/kg/day, i.p) as well as ZVAD (2 mg/kg/day, i.p) of LPS-induced renal failure and kidney pathology 3 or 24 h post LPS injection. Kidney content of interleukin-1β (IL-1β) and IL-10 were assessed. Oxidative stress as well as the RNA expression of neutrophil gelatinase-associated lipocalin (NGAL) and inhibitor of nuclear factor-kappa B (NF-κB) alpha (IκBα) in the kidney were also evaluated. Results: LPS augmented renal malondialdehyde and IL-10 levels as well as caspase-3 activity. However, it diminished the reduced glutathione and IL-1β levels; besides, it inhibited superoxide dismutase and catalase activities in the kidney. Histopathologic studies backed the previous observations. The studied agents significantly ameliorated LPS-induced alterations and suppressed acute kidney injury (AKI) by modulating NGAL and IκB-α mRNA levels. In conclusion, the present study suggested that the used drugs had potential beneficial role in sepsis prevention and its associated renal derangements.