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Master's Dissertation
DOI
10.11606/D.42.2012.tde-30012013-081433
Document
Author
Full name
João Paulo Limongi França Guilherme
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Moriscot, Anselmo Sigari (President)
Lopes, Marilene Hohmuth
Silva, Magnus Régios Dias da
Title in Portuguese
Efeitos de derivados do composto arylpyrazole (modulador seletivo do receptor de glicocorticóide) sobre a atrofia muscular esquelética.
Keywords in Portuguese
Atrofia muscular
Hormônios glicocorticóides
Músculo esquelético
Abstract in Portuguese
Neste estudo, testamos dois novos moduladores seletivos do receptor de glicocorticóide, nomeados L5 e L7, em comparação com o dexametasona, sobre aspectos estruturais, funcionais e moleculares no músculo sóleo. Ratos Wistar foram tratados com doses progressivas de dexametasona, L5 e L7 em 1 ou 7 dias. A massa corporal e a ingestão alimentar apresentaram queda após o tratamento com dexametasona em todas as doses; os tratamentos com L5/L7 mostraram resposta semelhante aos controles. O peso do músculo foi diminuído pelo dexametasona, efeito não observado nos tratamentos com L5/L7. Apenas o tratamento com dexametasona causou uma diminuição na área de secção transversa dos tipos de fibra muscular analisada. A força tetânica do sóleo foi diminuída pela dexametasona, nos tratamentos com L5/L7 este parâmetro também não foi afetado. A expressão gênica de MAFbx/Atrogin-1 e MuRF-1 foi elevada pela dexametasona; por outro lado, L5/L7 não elevaram a expressão destes genes. Concluímos que o L5/L7, em contraste com o dexametasona, preveniu o músculo esquelético da atrofia.
Title in English
In vivo effects of two novel arylpyrazole glucocorticoid receptor modulators on skeletal muscle structure and function.
Keywords in English
Glucocorticoid hormones
Muscle atrophy
Skeletal muscle
Abstract in English
In this study, we have tested two new selective modulators named L5 and L7 along with dexamethasone in skeletal muscle structural, functional and molecular aspects. Male Wistar rats were treated with progressive doses of dexamethasone, L5 and L7 for 1 and 7 days. While body weight and food intake were decreased by the dexamethasone treatment in all doses, L5/L7 treatments induced gain in body weight similarly to controls. Muscle weight was decreased by dexamethasone, while L5/L7 were ineffective. Only the dexamethasone treatment caused a decrease in the analyzed cross sectional area of the skeletal muscle fiber types. Soleus tetanic force was decreased by the dexamethasone treatment, while L5/L7 treatments did not alter this parameter. MAFbx/Atrogin-1 and MuRF-1 gene expressions were elevated by dexamethasone; on the other hand, L5/L7 did not modulate any expression of those genes. We conclude that L5/L7, in contrast to dexamethasone, spare skeletal muscle from structural and functional loss, and molecular changes, reinforcing their role as a therapeutic device.
 
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Publishing Date
2013-03-15
 
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