Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression

Autor(es)

do Vale, Gabriel T. ; Gonzaga, Natalia A. ; Simplicio, Janaina A. ; Tirapelli, Carlos R.

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 799, p. 33-40, MAR 15 2017.
• Citações Web of Science: 12

Resumo

We studied whether the beta(1-)adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10 mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O-2(-)) generation and thiobarbituric acid reactive substances (TSARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H2O2) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Noxl, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxol), c-Src, p47(Phox) or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) C delta and Racl. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKC delta and Racl, which are important activators of NADPH oxidase. (AU)

• Processo FAPESP: 15/22046-8 - Participação dos receptores AT1 no aumento da pressão arterial e do estresse oxidativo vascular induzidos pela abstinência ao etanol
• Beneficiário: Carlos Renato Tirapelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular