Moderate Intensity Physical Exercise Decreases Gastrocnemius Caspase-3 Expression on Mus musculus with Statin Treatment
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Keywords:
apoptosis, caspase-3, dyslipidemia, moderate intensity physical exercise, statin.
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Abstract
ABSTRACTIntroduction: Dyslipidemia is a lipid metabolism abnormality marked by increase or decrease of lipid fraction in the plasma. Statin or 3-Hydroxy-3-Methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor is an important dyslipidemia medication that may induce apoptosis of the skeletal muscle.Decrease of Bcl-2 and Bax ratio causing caspase-9 activation followed by caspase-3 activation occur in apoptosis. Moderate intensity physical exercise (MIPE) decreases DNA fragmentation, increases Bcl-2 protein level and decreases Bax transcript level.Methods: Thirty healthy BALB/C strain Mus musculus divided into 3 groups: first intervention group with statin only treatment (S), second intervention group with statin treatment plus MIPE using motorized treadmill (ST), and control (C) group with no statin and nor exercise. The duration of treatmentwas 28 days. Statin treatment dose was 2.06mg/kg bodyweight. Measurement caspase-3 was done by immunohistochemistry evaluation and the expression of capase-3 was calculated by cells count which expressing caspase-3.Results: There were more muscle cells expressing caspase-3 in the S group (47.00±12.92cells) than the C group (2.70±1.94 cells); p=0.000, the ST group (21.44±10.13 cells) than the C group (p=0.001), as well as S group and the ST group (p=0.000).Conclusion: Moderate intensity physical exercise can decrease caspase-3 expression in statin treated subject.Keywords: apoptosis, caspase-3, dyslipidemia, moderate intensity physical exercise, statin.
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Junita Jeanne Paliman, Ratna Darjanti Haryadi, Rwahita Satyawati Darmanta, Willy Sandhika, & Martha Kurnia Kusumawardani. (1). Moderate Intensity Physical Exercise Decreases Gastrocnemius Caspase-3 Expression on Mus musculus with Statin Treatment. Indonesian Journal of Physical Medicine and Rehabilitation, 10(01), 30 - 36. https://doi.org/10.36803/ijpmr.v10i1.281
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2. Accioly MF, Camargo Filho JC, Padulla SA, Lima AL, Bonfim MR, Carmo EM, et al. Effect of physical exercise and statins on the muscle function in animals with
dyslipidemia. Rev. Bras. de Medicina do Esporte 2012; 18(3): 198-202.
3. Dirks AJ, Jones KM. Statin-induced apoptosis and skeletal myopathy. Am J Physiol Cell Physiol 2006; 291(6): C1208-12.
4. Bonfim MR, Oliveira AS, Amaral SL, Monteiro HL. Treatment of dyslipidemia
with statins and physical exercises: recent findings of skeletal muscle responses. Arq Bras Cardiol 2015; 104(4): 324-31.
5. Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. The FASEB journal 2004; 18(10): 1150-2.
6. Schelman WR, Andres RD, Sipe KJ, Kang E, Weyhenmeyer JA. Glutamate mediates cell death and increases the Bax to Bcl-2 ratio in a differentiated neuronal cell line. Brain Res Mol 2004; 128(2): 160-9.
7. Southern WM, Nichenko AS, Shill DD, Spencer CC, Jenkins NT, McCully KK, et al. Skeletal muscle metabolic adaptations to endurance exercise training are attainable in mice with simvastatin treatment. PloS one 2017; 12(2): e0172551.
8. Ahmed S, Saber EA, Hamouda AH, Rifaai RA. Structural Changes in the Skeletal
Muscle Fiber of Adult Male Albino Rat Following Atorvastatin Treatment; the Possible Mechanisms of Atorvastatin Induced Myotoxicity. J Cytol Histol 2017; 8: 442.
9. Sacher J, Weigl L, Werner M, Szegedi C, Hohenegger M. Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells. J Pharmacol Exp Ther 2005; 314(3): 1032-41.
10. Bouitbir J, Daussin F, Charles AL, Rasseneur L, Dufour S, Richard R, et al. Mitochondria of trained skeletal muscle are protected from deleterious effects of statins. Muscle Nerve 2012; 46(3): 367-73.
11. Chung HR, Vakil M, Munroe M, Parikh A, Meador BM, Wu PT, et al. The impact of exercise on statin-associated skeletal muscle myopathy. PloS one 2016; 11(12): p.e0168065.