Statins are accustomed to prevent and deal with atherosclerotic coronary disease, however they also induce myopathy and mitochondrial dysfunction
October 2, 2020
Statins are accustomed to prevent and deal with atherosclerotic coronary disease, however they also induce myopathy and mitochondrial dysfunction. 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. = 12), atorvastatin-treated (ATO, = 12), and ATO plus aerobic exercise training group (ATO+EXE, = 12). All experimental procedures were approved by the Luteolin Institutional Animal Use and Care Committee of Kyung Hee University (KHUASP(SE)-16-064). 2.2. Atorvastatin Treatment Atorvastatin (Tahor??) was obtained from Pfizer (New York, NY, USA). The treatments were administered via oral gavage. The vehicle-treated rats received water in 0.25% w/v hydroxypropyl methylcellulose (HPMC), whereas the atorvastatin-treated rats received atorvastatin (5 mg kg?1 day?1) dissolved in 0.25% w/v HPMC, for 12 weeks. 2.3. Exercise Training The ATO+EXE group was trained for 12 weeks on a 15% incline, Luteolin 20 m min?1 for 60 min day?1, 5 days weekly?1, utilizing a rat home treadmill (Eco 3/6 treadmill; Columbus Instruments, Columbus, OH, USA), as previously reported [27,28]. 2.4. Forelimb Grip Strength Test After 12 weeks, a forelimb grip strength test was performed using an automated grip strength meter (Columbus Instruments). The rats were grasped by the bottom of the tail and hung onto the grip ring. After approximately 3 s, the rats were gently pulled towards the grip ring until they released their grip. The average grip strength force in grams was decided using a computerized electronic strain gauge mounted directly on the grip ring. We calculated the maximal forelimb strength from the average of three best trials, as previously reported . In addition, the fatigue index was measured by calculating the degree of fatigue by comparing the first two pulls to the last two pulls. Both values were normalized by body weight. 2.5. Oral Glucose Tolerance Test To measure the blood glucose level, which reflects insulin resistance, an oral glucose tolerance test (OGTT) was performed in all the groups after 12 weeks. Prior to OGTT, the rats fasted for 12 h and were orally administered a glucose solution (1.5 g kg?1 dissolved in sterile saline) by oral gavage. Blood samples were collected from the tail vein and the blood glucose level was measured before oral administration (0 min) and at 30, 60, and 120 min following oral administration, using an SD Code-Free blood glucose meter (SD BIOSENSOR, Inc., Suwon, Korea). 2.6. Western Blotting The soleus and white gastrocnemius muscles were homogenized in ice-cold lysis buffer (50 mM HEPES, 10 mM EDTA, 100 mM NaF, 50 mM Na pyrophosphate, 10 mM Na orthovanadate, and 1% Triton at pH 7.4), supplemented with protease/phosphatase inhibitor cocktails (Thermo Fisher Scientific, Waltham, MA, USA), using a Polytron homogenizer for 30 s. The protein concentration in the tissue lysates was decided using the bicinchoninic acid assay method. To evaluate the levels of Bax, Bcl-2, cleaved caspase-3, SOD1, SOD2, 0.05. 3. Results 3.1. Exercise Training Prevents Skeletal Muscle Fatigue in the Skeletal Muscles of Rats Treated with Atorvastatin In all groups, the final body weight of rats was significantly higher than the T initial weight. The ATO+EXE group had no effect on body weight (Physique 1A). We tested whether Luteolin exercise training attenuated the susceptibility to atorvastatin-induced glucose intolerance. Blood glucose levels were significantly lower in the ATO+EXE group than in the other groups throughout the 120 min duration of the ensure that you the area beneath the curve of blood sugar response ( 0.05; Body 1B,C). Serum CK amounts and exhaustion index had been higher in the ATO group than in the CON group considerably, whereas ATO+EXE attenuated these markers ( 0.05; Body 1D,E). Furthermore, maximal forelimb power was significantly low in the ATO group than in the CON group ( 0.05; Body 1F). Although a propensity towards a rise in maximal forelimb power was seen in ATO+EXE group, statistical significance had not been reached (= 0.137; Body 1F) Open up in another window Body 1 Workout schooling prevents skeletal muscle tissue exhaustion in the skeletal muscle groups of rats treated with atorvastatin. (A) Bodyweight; (B) Blood sugar; (C) Area beneath the.