Can Alfacalcidol ameliorate Atorvastatin-induced myopathy in adult male rats? A histological study

Abstract

Introduction: Atorvastatin (Ator), is the treatment of choice for reducing blood cholesterol. Most adverse effects associated with Statins therapy are muscle-related. Alfacalcidol (ALF), a vitamin D analog commonly used in osteoporosis; showed beneficial effects beyond the skeleton including muscle. Aim of the work: Investigating the possible protective effect of ALF in Atorvastatin induced myopathy in rats. Materials and Methods: Twenty-one adult male albino rats were divided equally into 3 groups: Group I (control). Group ΙΙ (Ator): received Atorvastatin (10 mg/kg/day). Group ΙΙΙ (Ator-ALF): received Ator concomitantly with Alfacalcidol (0.5 µg/kg/day). After 4 weeks of daily oral medications administration, blood samples from all rats were analyzed for creatine phosphokinase (CPK). The middle parts of biceps femoris muscles were processed for paraffin blocks for Hematoxylin and Eosin stain and cytochrome C immunohistochemical stain that subjected to morphometric and statistical studies. Moreover, resin blocks were processed for semithin and ultrathin sections examination. Results: In group II, light microscopic examination revealed fragmented and tapered muscle fibers, in addition to loss of regular pattern of transverse striation. Many fibers in transverse section acquired an irregular outline. Statistically, elevated CPK level, decreased mean muscle fiber diameter and increased mean area % of cytochrome C immunoreactivity compared to the control were recorded. Electron microscopic examination showed dissolution of many myofibrils and mitochondria either disfigured giant or with destructed cristae. However, group III showed muscle fibers that are almost comparable to the control group with clear transverse striations. That is confirmed statistically by decreased CPK level, increased mean muscle fiber diameter and decreased mean area % of cytochrome C immunoreactivity versus group II. While ultrastructurally, few areas of myofibrillar dissolution were noted. Conclusion:Alfacalcidiol has a protective effect on Ator induced myopathy confirmed by the biochemical analysis, light and electron microscopic examination as well as via morphometric studies.