Dexmedetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation.
Inflamm Res
; 66(5): 399-411, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28224201
ABSTRACT
OBJECTIVE AND DESIGN:
Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. MATERIALS Acute kidney injury in mice was induced by cisplatin. TREATMENTS Mice were administered with DEX 25 µg/kg or atipamezole 250 µg/kg (once a day, for 3 days) after cisplatin treatment.METHODS:
The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80+ macrophages, CD3+ T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.RESULTS:
DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1ß, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α2 adrenoceptor-dependent pathway.CONCLUSION:
We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substâncias Protetoras
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Dexmedetomidina
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Injúria Renal Aguda
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Anti-Inflamatórios
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article