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.

• Authors: Devadoss J Samuvel, Anandakumar Shunmugavel, Avtar K Singh, Inderjit Singh, Mushfiquddin Khan
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 68 Issue 10 Pg. 1310-9 (Oct 2016) ISSN: 2042-7158 [Electronic] England
• PMID: 27484743 (Publication Type: Journal Article)
• Copyright: © 2016 Royal Pharmaceutical Society.

Chemical References

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

Topics

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