The Impact of Exercise on Statin-Associated Skeletal Muscle Myopathy

Chung, Ho Kyoon; Vakil, Mayand; Munroe, Michael; Parikh, Alay; Meador, Benjamin M.; Wu, Pei Tzu; Jeong, Jin Hee; Woods, Jeffrey A.; Wilund, Kenneth R.; Boppart, Marni D.

doi:10.1371/journal.pone.0168065

Cited by 33 publications

(23 citation statements)

References 41 publications

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“…We found that atorvastatin induced an elevation in serum CK level and fatigue index and reduced maximal forelimb strength ( Figure 1 ). These results are consistent with previous findings which indicate that two weeks of statin treatment impairs skeletal muscle function, including reduced grip strength, maximal force, and fatigue [ 37 , 38 ]. In addition, we found that the skeletal muscles of rats treated with atorvastatin had a decreased muscle fiber cross-sectional area and an increased endomysium space ( Figure 2 ).…”

Section: Discussionsupporting

confidence: 93%

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

Seo

Heo

et al. 2020

JCM

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Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg−1 day−1) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca2+ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H2O2 emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles.

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Section: Discussionsupporting

confidence: 93%

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

Seo

Heo

et al. 2020

JCM

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“…In the last day of the experimental period, all animals were subjected to a grip strength test, as previously described (Chung et al, ). Briefly, mice were held up to the horizontal grip of a dynamometer and pulled steadily backwards until the researcher's strength matched the animal's maximum strength and they could not hold on any longer.…”

Section: Methodsmentioning

confidence: 99%

Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16‐transgenic mice

Santos

Moreira‐Pais

Neto

et al. 2019

Drug Development Research

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The nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) has been implicated in the progression of cancers induced by high‐risk human papillomaviruses (HPV). In cancer patients, NF‐κB is also thought to drive a chronic systemic inflammatory status, leading to cachexia. This study addressed the ability of dimethylaminoparthenolide (DMAPT), a water‐soluble NF‐κB inhibitor, to block the development of HPV‐induced lesions and wasting syndrome in HPV16‐transgenic mice. Mice received DMAPT orally (100 mg/kg/day), once a day, for 6 consecutive weeks. Body weight was monitored weekly along with food and water intake. After 6 weeks the animals were submitted to a grip strength test and sacrificed for specimen collection. Skin samples were analyzed histologically and for expression of NF‐κB‐regulated genes Bcl2 and Bcl2l1. Gastrocnemius muscles were weighted and analyzed for expression of NF‐κB subunits p50, p52, p65, and Rel‐B. DMAPT reduced the incidence of epidermal dysplasia (18.2% versus 33.3% in HPV16+/− untreated mice). This was associated with reduced expression of Bcl2 and Bcl2l1 (p = .0003 and p = .0014, respectively) and reduced neutrophilic infiltration (p = .0339). Treated mice also showed partially preserved bodyweight and strength, which were independent of the expression levels of NF‐κB subunits in skeletal muscle.These results suggest that NF‐κB inhibition may be a valid strategy against HPV‐induced lesions in vivo and warrant further preclinical tests particularly in the set of combination therapies. In addition, the data may support the use of DMAPT to prevent wasting syndrome.

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“…Exercise is recommended for those at risk of cardiovascular disease (i.e., those who take statins). However, there are reports that exercise reveals or exacerbates statin myalgia 13, 14 and myositis 12, 15, 16, and that statins limit training adaptations in skeletal muscle 57, 58. Therefore, we gave statin-treated and control rats access to an in-cage running wheel, which resulted in a type of voluntary exercise similar to that recommended for human subjects prescribed statins.…”

Section: Resultsmentioning

confidence: 99%