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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Coenzyme Q(10) protects against -cell toxicity induced by pravastatin treatment of hypercholesterolemia

Texto completo
Autor(es):
Lorza-Gil, Estela [1] ; de Souza, Jane C. [1] ; Garcia-Arevalo, Marta [1] ; Vettorazzi, Jean F. [1] ; Marques, Ana Carolina [1] ; Salerno, Alessandro G. [1] ; Trigo, Jose Roberto [2] ; Oliveira, Helena C. F. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Inst Biol, Dept Anim Biol, Campinas, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Journal of Cellular Physiology; v. 234, n. 7, p. 11047-11059, JUL 2019.
Citações Web of Science: 3
Resumo

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. (AU)

Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
Beneficiário:Licio Augusto Velloso
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 11/50400-0 - Metabolismo energético, estado redox e funcionalidade mitocondrial na morte celular e em desordens cardiometabólicas e neurodegenerativas
Beneficiário:Aníbal Eugênio Vercesi
Linha de fomento: Auxílio à Pesquisa - Temático