The possible promotive effect of Alfacalcidol on bone marrow derived mesenchymal stem cells in the treatment of Simvastatin induced myopathy in adult albino rats:Histological and immunohistochemical study

Background: Statins are the most popular type of anti-hyperlipidemic drugs.Benefits of statins in hypercholesterolemia management might be restricted by its myopathic side effects. Aim: This study set out to assess the myopathy (swelling) caused by simvastatin in rats and to find out whether there was any way to treat it by combining alfacalcidol with bone marrow mesenchymal stem cells. Methods: 45 adult male rats were divided into five groups each included 9 rats,Group Ⅰ(control),groupⅡ (Simvastatin induced Myopathy),group Ⅲ(Alfacalcidol),rats of these three groups were sacrificed at the 6th week,group Ⅳ(BM-MSCs),group Ⅴ(Alfacalcidol+BM-MSCs),rats of these two groups were sacrificed at 8th week.At the end of each experimental period before sacrifice, blood samples collected and analyzed for serum creatine kinase.Gastrocnemius muscle samples were prepared for histological and immunohistochemical examination.Results:Simvastatin-treated rats exhibited severe muscle degeneration, inflammation, and abnormal fiber structure.ALF treatment led to partial improvement, with some muscle fibers appearing normal.BM-MSCs treatment showed significant histological recovery, most fibers appearing normal with only limited damage.Combined ALF and BM-MSCs treatment closely restored normal muscle structure resembling control group.Results of Masson’s trichrome staining revealed excessive collagen in myopathy group,treatment groups showed reduced collagen deposition,especially the combination group.Immunohistochemistry showed strong myofibroblast reaction in myopathy group, reduced reaction in ALF and BM-MSCs groups, and minimal reaction in combination group.Serum CK levels, were highest in myopathy group;then in treatment groups,especially combined group, showed significant reduction.Conclusion:combined ALF and BM-MSCs therapy had better results than the use of stem cell therapy alone.