Olmesartan protects against oxidative stress possibly through the Nrf2 signaling pathway and inhibits inflammation in daunorubicin-induced nephrotoxicity in rats.
Int Immunopharmacol
; 18(2): 282-9, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24291173
ABSTRACT
Anthracycline anticancer drug daunorubicin (DNR) can induce chronic nephrotoxicity, which is believed to be based on oxidative injury. Olmesartan has significant blood pressure lowering effect via modulating renin-angiotensin system although its mechanism of action in DNR-induced renal injury is largely unknown. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in olmesartan-mediated antioxidant effects in DNR induced kidney cells. In addition, key factors involved in promoting inflammation and oxidative stress were studied. Sprague-Dawley rats were treated with a cumulative dose of 9 mg/kg DNR (i.v.). Olmesartan was administered orally every day for 6 weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was evaluated by measuring total cholesterol, triglyceride levels in kidney tissue and histopathological approaches; treatment with olmesartan reversed these changes. Furthermore, olmesartan treatment down-regulated phospho-MAPKAPK-2, caspase-12, p47(phox), p67(phox), upregulated renal expression of PPAR-γ, Bcl-xL, glutathione peroxidase and Nrf2. Furthermore, olmesartan down-regulated matrix metalloproteinase-2 and angiotensin II type I receptor expression in the kidney. In conclusion, the result demonstrated that angiotensin II and oxidative stress play a key role in DNR-induced nephrotoxicity. The present results indicated that olmesartan protects against oxidative stress, which may be possibly via the induction of Nrf2 signaling pathways.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetrazóis
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Bloqueadores do Receptor Tipo 1 de Angiotensina II
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Fator 2 Relacionado a NF-E2
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Imidazóis
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Nefropatias
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Anti-Inflamatórios
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article