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

Grant number: 12/23789-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Helga Cristina Almeida da Silva
Grantee:Pamela Vieira de Andrade
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The statins are currently considered the most useful agents for the treatment of hypercholesterolemia. In recent years, there have been reports of significant side effects in skeletal muscle, with myalgia, increases in serum creatine phosphokinase (CPK) and even rhabdomyolysis after using high doses of these medications. The early recognition of the myopathy induced by statins and its discontinuation is critical in preventing myopathy and decreasing possible sequels. The objectives of this study are: 1. To study the effect of statins on contraction and muscle contracture in rats exposed to low and high concentrations of the drug, 2. To correlate these changes with the morphology, biochemistry and protein expression in the muscle fiber and 3. To analyze the use of calcium channel release blocker (dantrolene) in this model. The study will be conducted on 50 male Wistar rats, divided into five groups: Group A - Control; , B - No statin with dantrolene (5 mg / kg), C - Statin low dose (5 mg / kg / day), D - Statin high dose (20 mg / kg / day), E - high dose statin (20 mg / kg / day) and dantrolene (5 mg / kg). The animals in groups C, D and E receive simvastatin daily, diluted with carboxy methyl cellulose (CMC) 0.5% by gavage for two months, and group A and B will receive only the vehicle (CMC) gavage for two months, the groups B and E will also receive dantrolene (5 mg / kg) subcutaneously for two months. The animals will be weighed weekly and will be recorded dietary intake; every seven days physical and neurological examinations will be performed. In vitro contracture tests will be performed - in which the contraction curves of each test will be analyzed to determine if there was contraction in the presence of halothane or caffeine - and tetanic stimulation test - which will be referred to as degree of contraction after each electrical stimulus. Further studies will be conducted at morphological, biochemical and molecular levels.

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