Pitavastatin ameliorates albuminuria and renal mesangial expansion by downregulating NOX4 in db/db mice.
Kidney Int
; 72(4): 473-80, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17568784
ABSTRACT
Recent studies have uncovered various pleiotrophic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase-inhibiting drugs (statins). Several studies have identified a beneficial effect of statins on diabetic nephropathy; however, the molecular mechanisms are unclear. In this study, we show that statin ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney. Pitavastatin treatment for 2 weeks starting at 12 weeks of age significantly reduced albuminuria in the db/db mice concomitant with a reduction of urinary 8-hydroxy-2'-deoxyguanosine and 8-epi-prostaglandin F(2alpha). Immunohistochemical analysis found increased amounts of 8-hydroxy-2'-deoxyguanosine and NOX4 protein in the kidney of db/db mice. Quantitative reverse transcription-polymerase chain reaction also showed increased levels of NOX4 mRNA. Pitavastatin normalized all of these changes in the kidneys of diabetic animals. Additionally, 12-week treatment with the statin completely normalized the levels of transforming growth factor-beta1 and fibronectin mRNA as well as the mesangial expansion characteristic of diabetic nephropathy. Our study demonstrates that pitavastatin ameliorates diabetic nephropathy in db/db mice by minimizing oxidative stress by downregulating NOX4 expression. These findings may provide insight into the mechanisms of statin therapy in early stages of diabetic nephropathy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Estresse Oxidativo
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
NADPH Oxidases
/
Diabetes Mellitus Tipo 2
/
Nefropatias Diabéticas
/
Albuminúria
/
Células Mesangiais
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2007
Tipo de documento:
Article