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|Title:||Coenzyme Q(10) protects against -cell toxicity induced by pravastatin treatment of hypercholesterolemia|
de Souza, Jane C.
Vettorazzi, Jean F.
Marques, Ana Carolina
Salerno, Alessandro G.
Trigo, Jose Roberto
Oliveira, Helena C. F.
|Abstract:||New onset of diabetes is associated with the use of statins.We have recently demonstrated that pravastatin-treated hypercholesterolemic LDL receptor knockout (LDLr-/-) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q (10) (CoQ (10)), an intermediate generated in the cholesterol synthesis pathway. LDLr (-/-) mice were treated with pravastatin and/or CoQ (10) for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ (10) content. Dietary CoQ (10) supplementation of pravastatin-treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2-fold), and fully restored islet glucose-stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild-type mice. In vitro, insulin-secreting INS1E cells cotreated with CoQ (10) were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose-dependent INS1E cell death (10-15-fold), which were also attenuated by CoQ (10) cotreatment. Together, these results demonstrate that statins impair -cell redox balance, function and viability. However, CoQ (10) supplementation can protect the statins detrimental effects on the endocrine pancreas|
|Editor:||John Wiley & Sons|
|Appears in Collections:||IB - Artigos e Outros Documentos|
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