Abstract
Simvastatin is one of the most common medicines prescribed to treat human hypercholesterolemia. Simvastatin acts through the inhibition of cholesterol synthesis. Unfortunately, simvastatin causes unwanted side effects on muscles, such as soreness, tiredness, or weakness. Therefore, to understand the mechanism of action of simvastatin, it is important to study its physiological and structural impacts on muscle in varied animal models. Here we report on the effects of simvastatin on two biological models: zebrafish embryos and chicken muscle culture. In the last years, our group and others showed that simvastatin treatment in zebrafish embryos reduces fish movements and induces major structural alterations in skeletal muscles. We also showed that simvastatin and membrane cholesterol depletion induce major changes in proliferation and differentiation of muscle cells in chick muscle cultures. Here, we review and discuss these observations considering reported data on the use of simvastatin as a potential therapy for Duchenne muscular dystrophy.
Highlights
High cholesterol levels in the blood are associated with an increased risk of cardiovascular disease in humans
Our lab has been exploring the optical transparency of the zebrafish embryo by using high-resolution fluorescence microscopy, which enables us to do a thorough structural analysis of the distribution of key muscle proteins during somite formation (Costa et al, 2002, 2008)
After this characterization of normal myogenesis, we showed that simvastatin causes several alterations in zebrafish embryos, such as body shortening and bending, depending on the dose (Campos et al, 2015, 2016)
Summary
High cholesterol levels in the blood are associated with an increased risk of cardiovascular disease in humans. Statins have been the number one choice of physicians to control blood cholesterol levels since these drugs inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA), a key enzyme of the cholesterol biosynthetic pathway. Simvastatin effectively decreases blood cholesterol levels and the risk of heart problems in those at high risk. Simvastatin can induce myalgia, myopathy, and rhabdomyolysis (Nikolic et al, 2020; Turner and Pirmohamed, 2019). To further analyze the effects of statins in muscle at the cellular level, our group has been studying the effects of simvastatin treatment in zebrafish (Danio rerio) embryos. Zebrafish is a vertebrate biological model with several advantages, such as a well-characterized genome, easy of maintenance in laboratory conditions, and fast growth (Horzmann and Freeman, 2018)
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