Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice

Abstract Statins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional chan...

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Autores principales:	Juan C. Díaz-Zagoya, Alejandro Marín-Medina, Alma M. Zetina-Esquivel, Jorge L. Blé-Castillo, Andrés E. Castell-Rodríguez, Isela E. Juárez-Rojop, Rodrigo Miranda-Zamora
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99bc8dd425344a31b26bced42afc131b
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spelling	oai:doaj.org-article:99bc8dd425344a31b26bced42afc131b2021-12-02T14:53:35ZEffects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice10.1038/s41598-021-95140-12045-2322https://doaj.org/article/99bc8dd425344a31b26bced42afc131b2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95140-1https://doaj.org/toc/2045-2322Abstract Statins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional changes on hepatocyte mitochondria. In a mouse model we studied the combined administration of a cholesterol-rich diet along with mild and moderate doses of rosuvastatin (1, 2.5 or 5 mg/kg/day) during several days. After the animals were sacrificed, liver mitochondria were isolated for microscopic studies and to analyze the respiratory function. The respiratory control (state-3/state-4) was evaluated in mice who received high doses of rosuvastatin. Rosuvastatin doses higher than 20 mg/kg/day induced premature death in mice with a hypercholesterolemic diet, but not in mice with a cholesterol-free diet. Doses from 2.5 to 5 mg/kg/day also induced morphological and functional alterations in mitochondria but these hypercholesterolemic animals survived longer. Giving 1 mg/kg/day, which is close to the maximal therapeutic dose for humans, did not affect mitochondrial architecture or respiratory function after two months of treatment. We analyzed the effect of rosuvastatin on hepatic tissue because it is where statins are mainly accumulated and it is the main site of endogenous cholesterol synthesis. Our results contribute to understand the side effects of rosuvastatin in hypercholesterolemic mice, effects that could also affect humans who are intolerant to statins.Juan C. Díaz-ZagoyaAlejandro Marín-MedinaAlma M. Zetina-EsquivelJorge L. Blé-CastilloAndrés E. Castell-RodríguezIsela E. Juárez-RojopRodrigo Miranda-ZamoraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juan C. Díaz-Zagoya Alejandro Marín-Medina Alma M. Zetina-Esquivel Jorge L. Blé-Castillo Andrés E. Castell-Rodríguez Isela E. Juárez-Rojop Rodrigo Miranda-Zamora Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
description	Abstract Statins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional changes on hepatocyte mitochondria. In a mouse model we studied the combined administration of a cholesterol-rich diet along with mild and moderate doses of rosuvastatin (1, 2.5 or 5 mg/kg/day) during several days. After the animals were sacrificed, liver mitochondria were isolated for microscopic studies and to analyze the respiratory function. The respiratory control (state-3/state-4) was evaluated in mice who received high doses of rosuvastatin. Rosuvastatin doses higher than 20 mg/kg/day induced premature death in mice with a hypercholesterolemic diet, but not in mice with a cholesterol-free diet. Doses from 2.5 to 5 mg/kg/day also induced morphological and functional alterations in mitochondria but these hypercholesterolemic animals survived longer. Giving 1 mg/kg/day, which is close to the maximal therapeutic dose for humans, did not affect mitochondrial architecture or respiratory function after two months of treatment. We analyzed the effect of rosuvastatin on hepatic tissue because it is where statins are mainly accumulated and it is the main site of endogenous cholesterol synthesis. Our results contribute to understand the side effects of rosuvastatin in hypercholesterolemic mice, effects that could also affect humans who are intolerant to statins.
format	article
author	Juan C. Díaz-Zagoya Alejandro Marín-Medina Alma M. Zetina-Esquivel Jorge L. Blé-Castillo Andrés E. Castell-Rodríguez Isela E. Juárez-Rojop Rodrigo Miranda-Zamora
author_facet	Juan C. Díaz-Zagoya Alejandro Marín-Medina Alma M. Zetina-Esquivel Jorge L. Blé-Castillo Andrés E. Castell-Rodríguez Isela E. Juárez-Rojop Rodrigo Miranda-Zamora
author_sort	Juan C. Díaz-Zagoya
title	Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
title_short	Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
title_full	Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
title_fullStr	Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
title_full_unstemmed	Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
title_sort	effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/99bc8dd425344a31b26bced42afc131b
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Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice

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