Open AccessS‐Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of lipopolysaccharide‐induced sepsis
Author(s) -
Samuvel Devadoss J.,
Shunmugavel Anandakumar,
Singh Avtar K.,
Singh Inderjit,
Khan Mushfiquddin
Publication year - 2016
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12608
Subject(s) - lipopolysaccharide , sepsis , creatinine , medicine , endocrinology , kidney , acute kidney injury , nitric oxide , blood urea nitrogen , inflammation , nitric oxide synthase , lymphocyte , pharmacology
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, i NOS ) 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 i NOS 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.