S-Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of lipopolysaccharide-induced sepsis

Abstract

Objective: Sepsis induces an inflammatory response that results in acute renal failure (ARF). The current study is to evaluate the role of S-Nitrosoglutathione (GSNO) in renoprotection from lipopolysaccharide (LPS)-induced sepsis. Methods: Rats were divided to three groups. First group received LPS (5 mg/kg body weight), second group was treated with LPS + GSNO (50 μg/kg body weight), and third group was administered with vehicle (saline). They were sacrificed on day 1 and 3 post-LPS injection. Serum levels of nitric oxide (NO), creatinine and blood urea nitrogen (BUN) were analysed. Tissue morphology, T lymphocyte infiltrations, and the expression of inflammatory (TNF-α, iNOS) and anti-inflammatory (IL-10) mediators as well as glutathione (GSH) levels were determined. Key finding: Lipopolysaccharide significantly decreased body weight and increased cellular T lymphocyte infiltration, caspase-3 and iNOS and decreased PPAR-γ in renal tissue. NO, creatinine and BUN were significantly elevated after LPS challenge, and they significantly decreased after GSNO treatment. TNF-α level was found significantly increased in LPS-treated serum and kidney. GSNO treatment of LPS-challenged rats decreased caspase-3, iNOS, TNF-α, T lymphocyte infiltration and remarkably increased levels of IL-10, PPAR-γ and GSH. Conclusion: GSNO can be used as a renoprotective agent for the treatment of sepsis-induced acute kidney injury.