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Effects of Estrogen on Statin‐Induced Myotoxicity in Vitro
Author(s) -
Roussel Jaclyn,
Stambersky Ashten,
Ball Karen L.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.856.6
Subject(s) - simvastatin , apoptosis , myotoxin , in vitro , statin , estrogen , chemistry , c2c12 , myocyte , endocrinology , medicine , andrology , biochemistry , phospholipase a2 , enzyme , myogenesis
In vitro studies have suggested a greater statin‐induced myotoxicity in females. This is in contrast to what would be predicted based on estrogen (E) protection against other models of muscle damage. Therefore, the purpose of this study was to examine estrogen effects in an in vitro model of statin‐induced myotoxicity. C2C12 myoblasts were plated at a density of 0.15×10 5 cells in a 6‐well plate and maintained in growth media (GM) until 80%–100% confluence. Media was then replaced with differentiation media (DM) and cells allowed to differentiate for seven days. Differentiated cells were then exposed to Simvastatin (SS;10 −4 mM), E alone (0.1 μM or 0.01 μM), or SS+E. After 48 hours, light microscopic images were taken to measure multinucleated cell numbers and fiber diameters. At 72 hours, immunofluorescence was performed to identify myosin positive cells and apoptotic nuclei. The SS induced toxicity was consistent with previous studies. Fiber diameters were decreased (45.7±4.1 μm vs 16.0±1.8 μm*) with significant increase in apoptotic nuclei (17%±1.4% vs 55.3%±4.3%*). Interestingly, the effects of E in combination with SS were dependent on the parameters measured. Whereas E produced a protective trend with greater fiber diameters (23.7±5.4 μm vs 16.0±1.8 μm;NS), E exacerbated the SS impact on apoptosis (74%±6.4%–87%±8.1% vs 55.3%±4.3%*). In conclusion, our data revealed contradictory influences of E on statin‐induced myotoxicity. Clarification of estrogen's effect could have significance in understanding gender specific adverse clinical responses to stain therapy. *p<0.05 Support or Funding Information The Herbert H. and Grace A. Dow Foundation This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .