Morphofunctional, biochemical and molecular analysis in experimental model of myopathy associated with statin

• Grant number: 12/21267-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2013
• End date: September 30, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Helga Cristina Almeida da Silva
• Grantee: Helga Cristina Almeida da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Acary Souza Bulle Oliveira ; Ismael Dale Cotrim Guerreiro da Silva ; Itamar Souza de Oliveira-Júnior ; Joilson Moura dos Santos ; Pamela Vieira de Andrade

Abstract

The treatment of dyslipidemia received great impetus after the development of drugs that, alongside dietary measures, contribute to the reduction of serum lipids. Among these drugs are the statins, currently considered the most useful agents for the treatment of hypercholesterolemia. The statin therapy may be severely limited by side effects involving many tissues, particularly skeletal muscle. In recent years, there have been increased reports of significant side effects in skeletal muscle, with myalgia, increased serum levels of creatine phosphokinase (CPK) and even rhabdomyolysis after high doses of these medications. The muscle biopsy may reveal muscle fiber necrosis, atrophy of type II fibers or increased lipid storage. However, some authors have reported changes consistent with mitochondrial myopathy in some patients with cox-negative fibers and ragged red fibers. Early recognition of myopathy induced by statins and their discontinuation is essential to the prevention of myopathy and to decrease possible sequels.The study will be conducted with 30 male Wistar rats, which will be divided into three groups: A - Control group, B - low-dose statin group (5 mg / kg / day), C - high dose statin group (20 mg / kg / day). The animals will be housed in individual cages and will be given water and commercial feed ad libitum. The animals of groups B and C will receive daily simvastatin, diluted with carboxymethyl cellulose (CMC) 0.5% by gavage for two months. The animals of group A will receive only the vehicle (CMC) by gavage for two months. The animals will be weighed weekly, and the consumption of solid and liquid diet will be registered; every seven days will be performed physical and neurological examinations.Analysis will include the in vitro contracture test - in which the contraction curves of each test will be analyzed to determine if there was contracture, defined as abnormal elevation of the baseline in the presence of halothane or caffeine - and tetanic stimulation test - where the result of the test will be referred as degree of contraction after each electrical stimulus. Further studies will be conducted at morphological, biochemical and molecular levels. The characterization of this model will allow its use in the future to study the effects of statin use in anesthesia. (AU)