Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS/NO signaling pathway in rats.
Nitric Oxide
; 85: 1-9, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30659917
ABSTRACT
Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30⯵g/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10â¯mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15â¯mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α2-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α2-ARs instead of IRs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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Dexmedetomidina
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Óxido Nítrico Sintase Tipo II
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Injúria Renal Aguda
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Agonistas de Receptores Adrenérgicos alfa 2
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Nitric Oxide
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article