Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin

Gadbut, Albert P.; Caruso, Anthony P.; Galper, Jonas B.

doi:10.1016/s0022-2828(95)92163-x

Cited by 61 publications

(13 citation statements)

References 12 publications

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“…These statins had similar adverse event risks from a meta-analysis of statin trials [3], similar adverse event rates from postmarketing reports [13], and similar toxicity concentrations to initiate lethality to muscle cells in tissue culture [14]. Moreover, no cases had exposures to any other statins.…”

Section: Methodsmentioning

confidence: 85%

Statin and statin–fibrate use was significantly associated with increased myositis risk in a managed care population

McClure

Valuck

Glanz

et al. 2007

Journal of Clinical Epidemiology

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Section: Methodsmentioning

confidence: 85%

Statin and statin–fibrate use was significantly associated with increased myositis risk in a managed care population

McClure

Valuck

Glanz

et al. 2007

Journal of Clinical Epidemiology

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“…Some statins, such as cerivastatin, have especially marked toxicity in skeletal muscle and have been removed from clinical use (1,4). It has been suggested that more hydrophilic inhibitors, e.g., pravastatin, may be less toxic (14,57); however, other studies have not found a clear connection between lipophilicity and toxicity (58, 59). Several nitrogencontaining bisphosphonates, such as alendronate and risedronate, are also known to inhibit enzymes of the mevalonate pathway (60).…”

Section: Discussionmentioning

confidence: 99%

The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity

Hanai¹,

Cao²,

Tanksale³

et al. 2007

J. Clin. Invest.

176

218

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Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and are widely used to treat hypercholesterolemia. These drugs can lead to a number of side effects in muscle, including muscle fiber breakdown; however, the mechanisms of muscle injury by statins are poorly understood. We report that lovastatin induced the expression of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with statin myopathy, in zebrafish embryos, and in vitro in murine skeletal muscle cells. In cultured mouse myotubes, atrogin-1 induction following lovastatin treatment was accompanied by distinct morphological changes, largely absent in atrogin-1 null cells. In zebrafish embryos, lovastatin promoted muscle fiber damage, an effect that was closely mimicked by knockdown of zebrafish HMG-CoA reductase. Moreover, atrogin-1 knockdown in zebrafish embryos prevented lovastatin-induced muscle injury. Finally, overexpression of PGC-1α, a transcriptional coactivator that induces mitochondrial biogenesis and protects against the development of muscle atrophy, dramatically prevented lovastatin-induced muscle damage and abrogated atrogin-1 induction both in fish and in cultured mouse myotubes. Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins.

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“…Atorvastatin is a lipophilic statin (Igel et al., ) increasing its ability to penetrate into peripheral tissues (Hamelin & Turgeon, ). In vitro (Gadbut et al., ) and in vivo (Nakahara et al., ) experiments suggest that lipophilic agents are more likely to produce muscular effects than hydrophilic compounds.…”

mentioning

confidence: 99%

No adverse effects of statins on muscle function and health‐related parameters in the elderly: An exercise study

Panayiotou

Paschalis

Nikolaidis

et al. 2012

Scandinavian Med Sci Sports

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The aim of the present study was to investigate the effects of a repeated bout of eccentric exercise on health-related parameters and muscle performance on subjects undergoing atorvastatin therapy. Twenty-eight elderly men participated in the investigation and were assigned either in a control (n = 14) or in a statin therapy group (n = 14). All participants performed two isokinetic eccentric exercise bouts separated by 3 weeks. Muscle damage indices, resting energy expenditure, substrate metabolism, lipid and lipoprotein profile, as well as insulin sensitivity, were evaluated before and after eccentric. No differences in muscle function were observed between the two groups either at rest or after exercise. Eccentric exercise increased resting energy expenditure, increased fat oxidation, improved lipid profile, and increased insulin resistance 2 days after both eccentric exercise bouts. However, these changes appeared to lesser extent after the second bout. No differences were observed in the responses in the health-related parameters in the control and in the statin therapy group. Eccentric exercise affected similarly the control and the atorvastatin-treated individuals. The present results indicate that atorvastatin-treated elderly individuals may participate in various physical activities, even high-intensity muscle-damaging activities, without negative impact on muscle function and adaptation.

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Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin

Cited by 61 publications

References 12 publications

Statin and statin–fibrate use was significantly associated with increased myositis risk in a managed care population

Statin and statin–fibrate use was significantly associated with increased myositis risk in a managed care population

The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity

No adverse effects of statins on muscle function and health‐related parameters in the elderly: An exercise study

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