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

J Pharm Pharmacol. 2016 Oct;68(10):1310-9. doi: 10.1111/jphp.12608. Epub 2016 Aug 3.

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.

Keywords: S-Nitrosoglutathione; acute kidney injury; lipopolysaccharide; renoprotection; sepsis.

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Blood Urea Nitrogen
  • Caspase 3 / metabolism
  • Creatinine / blood
  • Female
  • Glutathione / metabolism
  • Interleukin-10 / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Lipopolysaccharides / pharmacology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • S-Nitrosoglutathione / pharmacology*
  • Sepsis / blood
  • Sepsis / chemically induced*
  • Sepsis / drug therapy*
  • Sepsis / metabolism
  • T-Lymphocytes / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Nitric Oxide
  • S-Nitrosoglutathione
  • Creatinine
  • Nitric Oxide Synthase Type II
  • Caspase 3
  • Glutathione