Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats

Schaefer, William H.; Lawrence, Jeffery W; Loughlin, Amy F; Stoffregen, Dana A.; Mixson, Lori; Dean, Dennis C.; Raab, Conrad E.; Yu, Nathan X.; Lankas, George R.; Frederick, Clay B.

doi:10.1016/j.taap.2003.08.013

Cited by 123 publications

(93 citation statements)

References 31 publications

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“…Degeneration and inflammatory cellular infiltration in skeletal muscle fibers were noticed in this study. This was reported by many investigators using a variety of statins [16,7,17]. It could be suggested that the degenerative changes that affected the muscle fibers might be the stimulus that initiated the inflammatory reaction.…”

Section: The Morphometric Resultsmentioning

confidence: 79%

“…These histological findings were in a good agreement with Westwood et al, [11] who found that muscles showing the most severe necrosis following administration of statin contained a substantial proportion of type II fibers, and in these muscles it was the type II fibers that become degenerated first and the type I fibers were least sensitive to statins. The observation that statin myotoxicity affects type II, glycolytic muscle fibers more than type I, oxidative fibers [16] could be explained by decreased mitochondrial number/function in pale, glycolytic muscle enhances susceptibility to muscle damage and wasting. This observation could be also explained by the protective effect of PGC-1α gene expression which is greater in oxidative fibers [13].…”

Section: The Morphometric Resultsmentioning

confidence: 99%

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Structural Changes in the Skeletal Muscle Fiber of Adult Male Albino Rat Following Atorvastatin Treatment; the Possible Mechanisms of Atorvastatin Induced Myotoxicity

Mokhmer¹,

Saber²,

Hamouda³

et al. 2017

J Cytol Histol

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Section: The Morphometric Resultsmentioning

confidence: 79%

Section: The Morphometric Resultsmentioning

confidence: 99%

Structural Changes in the Skeletal Muscle Fiber of Adult Male Albino Rat Following Atorvastatin Treatment; the Possible Mechanisms of Atorvastatin Induced Myotoxicity

Mokhmer¹,

Saber²,

Hamouda³

et al. 2017

J Cytol Histol

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“…Schaefer et al (2004) previously reported induction skeletal myopathy in type-2 muscle fibers of rats by cerivastatin. They also described mitochondrial alteration, including disorganized cristae, flocculent matrix material, and membranous whorls in myofibers with degeneration.…”

Section: Introductionmentioning

confidence: 94%

Skeletal Muscle Susceptibility to Clofibrate Induction of Lesions in Rats

et al. 2007

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Morphological changes induced by clofibrate in type-1 predominant soleus, type-2 predominant tensor fasciae latae, and type-1 and -2 mixed biceps femoris muscles and diaphragm in rats were investigated. Administration of the agent at 500 or 750 mg/kg/day by oral gavage for 14 or 28 days caused lesions in the soleus muscle and diaphragm, bur no changes in the tensor fasciae latae and biceps femoris muscles. In soleus muscle, vacuolation of muscle fibers was observed in all animals treated with clofibrate, and degeneration of muscle fibers and infiltration of leukocytes were noted at 750 mg/kg/day. In diaphragm, vacuolation of muscle fibers was also observed in all animals treated with clofibrate, and these lesions were located in type-1 skeletal muscles densely stained with NADH-TR. The vacuoles seen in soleus muscle and diaphragm were positive for oil red O staining. In addition, increase of lipid droplets and mitochondrial hypertrophy was seen in soleus muscle, ultrastructurally. These data suggest that sensitivity to clofibrate-induced muscle toxicity differs among muscles, with type-1 fibers being susceptible.

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“…The evidence in research indicates that the mitochondrial harm could probably interfere in the regulation of cytosolic calcium, leading to the onset of apoptotic and degenerative processes which would explain the muscular injuries by the statins 23,25 . In fact, some research points that the use of statins leads to mitochondrial injury, either being a primary or secondary factor in the muscular injury [26][27][28] . Moreover, in that context, many drugs, including statins, are excreted in the bile and urine.…”

Section: Discussionmentioning

confidence: 99%

Efeito do exercício físico e estatinas na função muscular em animais com dislipidemia

Accioly

Filho

Padulla

et al. 2012

Rev Bras Med Esporte

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As estatinas são utilizadas no tratamento das dislipidemias, com grande tolerância; no entanto, vários efeitos colaterais podem surgir, destacando-se miopatia. A prática regular do exercício físico (EF) produz modificações favoráveis no perfil lipídico; entretanto, pode gerar lesões musculares. OBJETIVO: Avaliar o efeito da associação entre exercício físico e estatinas na função muscular, pela análise histológica, em modelo experimental animal com dislipidemia. MÉTODOS: Foram utilizados 80 ratos machos Wistar, distribuídos em oito grupos, incluindo animais submetidos à dieta hipercolesterolêmica (DH), sinvastatina com (G1) e sem (G2) EF; DH e fluvastatina, com (G3) e sem EF (G4); alimentados com ração comercial (RC) na presença (G5) e ausência de (G6) EF; DH submetidos (G7) ou não (G8) a EF. A DH foi administrada por 90 dias, as estatinas e prática de EF em esteira rolante por oito semanas. Os animais foram sacrificados, e o músculo sóleo retirado para análise histológica. Aplicaram-se os testes t de Student pareado e análise multivariada, com nível significante para p < 0,05. RESULTADOS: As principais alterações histológicas encontradas foram fibras de diferentes diâmetros, atróficas, em degeneração, splitting, edema, infiltrado inflamatório. Essas alterações foram observadas em 90% dos animais do grupo G1, 80% do G2, 70% do G3, 30% do G4, 40% do G5 e 30% do G7. Nos grupos G6 e G8 identificaram-se fibras musculares com morfologia preservada. CONCLUSÕES: Na avaliação histológica muscular, a associação entre fluvastatina, sinvastatina e exercício físico acarreta alterações morfológicas com predomínio no uso da sinvastatina, variando de grau leve a grave, no músculo sóleo de ratos, induzidos pelos inibidores da HMG-CoA redutase.

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Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats

Cited by 123 publications

References 31 publications

Structural Changes in the Skeletal Muscle Fiber of Adult Male Albino Rat Following Atorvastatin Treatment; the Possible Mechanisms of Atorvastatin Induced Myotoxicity

Structural Changes in the Skeletal Muscle Fiber of Adult Male Albino Rat Following Atorvastatin Treatment; the Possible Mechanisms of Atorvastatin Induced Myotoxicity

Skeletal Muscle Susceptibility to Clofibrate Induction of Lesions in Rats

Efeito do exercício físico e estatinas na função muscular em animais com dislipidemia

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