PREVENTIVE EFFECT OF LONG ACTING Β2-AGONISTS ON STATIN INDUCED MYOPATHIES

Β2-Agonists on Statin Induced Myopathies

Abstract

Objective: To identify the histological effectsof statin-induced skeletal muscle myopathy in a Rat model and to
find protective effect of long acting β2-agonists.
Study Design: Laboratory based experimental randomized controlled trial.
Place and Duration of Study: Study was conducted at the department of Anatomy, Army Medical College
Rawalpindi in collaboration with National Institute of Health (NIH) Islamabad and Armed forces institute of
Pathology (AFIP) Rawalpindi, from Jan 2015 to Jun 2016.
Material and Methods: Adult male Sprague-Dawley rats were procured from NIH Islamabad. Their average
approximate age was 70-80 days and weight range was 250 ± 50 grams. The animals were randomly selected and
divided into three groups. Group A was the control. Each rat of group B received Simvastatin dissolved in
distilled water, by oral gavage (60mg/kg/day) once daily, for 12 weeks. Animals of group C received simvastatin
dissolved in distilled water, (60mg/kg/day) once daily plus formoterol dissolved in distilled water (3μg/kg/day)
once daily for 12 weeks. Both were administered with the help of oral gavage. The animals were sacrificed after
three months of the experimental period. Extensor digitorum longus (EDL) tendon was isolated and dissected
out. Tissue processing was done on the EDL muscle followed by Haematoxylin and Eosin staining. Fiber crosssectional
areas, Number of myofibers and Central Myonuclei were counted per high power field in each
specimen of all three groups.
Results: Examination of H&E stained sections of the extensor digitorum longus muscle of the control group
revealed the histological structure of skeletal muscle. Cross sectional area of myofibers and number of myofibers
were significantly lower in group B as compared to the control group A. Group C showed significant increase in
cross sectional area of myofibers and number of myofibers as compared to group B. No central myonuclei was
seen in any section.
Conclusion: Simvastatin induced the histomorphological changes in the skeletal muscle of experimental rats by
reducing myofiber size and number. Formoterol co-administration minimized simvastatin induced myopathy by
significantly increasing myofiber size and number.