LPS-challenged mice kidney and modulatory effect of Simvastatin

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Author: 
Maha A. Rabie, Nihad I. Eid, Mohammed M. Nooh and Sanaa A. Kenawy
Abstract: 

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-induced 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.

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