Full Length Research Article LPS - CHALLENGED MICE KIDNEY AND MODULATORY EFFECT OF SIMVASTATIN

Background: Lipopolysaccharide (LPS) is recognized by the innate immune system. This study was designed to investigate the effects of simvastatin on LPS - induced renal oxidative and immunological changes of mice. Methods: Male Swiss mice were injected with LPS (1 mg/kg; i.p.) and the effects of pretreatment with simvastatin (10 mg/kg; i.p.) on LPS - induced renal failure and kidney pathology were examined 3 hours post LPS injection. Plasma concentrations of urea, creatinine and lactate dehydrogenase (LDH) activity as well as kidney contents 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 markedly increased plasma urea and creatinine levels as well as LDH activity. Furthermore, 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. Simvastatin pretreatment significantly ameliorated LPS - indu ced alterations and suppressed acute kidney injury (AKI) by modulating NGAL and IκB - α mRNA levels. Conclusion: The present study suggests that simvastatin has potential beneficial role in sepsis prevention and its associated renal derangements.