SIMVASTATIN INDUCED HISTOMORPHOLOGICAL CHANGES IN SKELETAL MUSCLE FIBER OF RATS AND PROTECTIVE EFFECT OF FORMOTEROL COADMINISTRATION
Keywords:Formoterol, Myopathy, Skeletal muscle, Statin
Objective: To study Simvastatin induced, qualitative histomorphological changes in skeletal muscle fibers of rats and find protective effect of Formoterol co-administration in Simvastatin induced myopathy.
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 with weight as 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 Hematoxylin and Eosin staining. Fiber variability,
inflammation, necrosis, shape of nuclei and location of nuclei were assessed per high power field in each specimen of all the groups.
Results: Examination of H&E stained sections of the extensor digitorum longus muscle of the control group revealed the normal structure of skeletal muscle. Fiber variability, inflammation and necrosis were significantly higher in group B as compared to the control group A. Group C showed significantly decrease in myofiber variability, inflammation and necrosis in myofibers as compared to group B.
Conclusion: Simvastatin induced the histomorphological changes in the skeletal muscle of experimental rats by increasing myofiber variability, inflammation and necrosis. Formoterol co-administration minimized the simvastatin induced myopathy by significantly decreasing myofiber variability, inflammation and necrosis.