Made available in DSpace on 2014-12-17T14:16:29Z (GMT). No. of bitstreams: 1 FranciscoPFN_DISSERT.pdf: 3112782 bytes, checksum: 175f8b00518f556ca96ea9b6dd10eeb7 (MD5) Previous issue date: 2010-02-22 / Bone is a dynamic tissue that is in constant process of remodeling in response to mechanical stress and hormonal changes. This study aimed to understand the relationship between the biochemical changes, which women in the menopausal transition are subject to, and how the use of an alternative therapy with lipoic acid (LA) could influence these changes. The study of double-blind, was carried out in perimenopausal women that underwent a three month treatment with 600 mg of AL compared with another group that received placebo during the same period. This study showed that women had a waist circunference and body mass index above the values recommended by WHO (WC &#8805; 80 cm; BMI > 25kg/m2). Associated with this, these women had increased concentrations of total cholesterol and triglycerides, and borderline LDL (Total Cholesterol > 200mg/dL; Triglycerides > 150mg/dL; LDL >130mg/dL). These changes were not affected by treatment with AL. There were no shifts in liver profile (ALT, AST and GGT), kidney profile (urea, creatinine, total protein and albumin), mineral profile (Total Calcium, Ionized Calcium, Phosphorus and Magnesium) as well in bone markers (osteocalcin, Total Alkaline Phosphatase and Tartrate Resistant Acid Phosphatase) after treatment with LA. The results of the oxidative profile showed that treatment with LA decreased GPx activity (p < 0,01), while for the TBARS, GSH and SOD activity there were no differences. With regard to SOD, this enzyme will submit to be high in the placebo group after 3 months of study (p<0,05). The expression of RANKL mRNA was reduced (p < 0,05) and of RANK increased (p <0.001), after treatment with LA, while the expression of IL-6 and TNF-&#593; genes were no changed. We conclude that women already in the perimenopause stage have changes in lipid profile and body composition that could induce shifts in oxidative and bone metabolism. However, LA treatment has provided an effective effect in the oxidative and bone profile since the earliest markers such as GPx activity and mRNA expression of RANKL, respectively, were reduced associated with no change in SOD activity. These results suggest a beneficial and protective effect of LA, indicating it potential as an alternative treatment to help the to prevent the complications associated with estrogen deficiency / O osso ? um tecido din?mico que est? em constante processo de remodela??o em resposta ao estresse mec?nico e mudan?as hormonais. O presente trabalho teve por objetivo entender a rela??o entre as altera??es bioqu?micas, oxidativas e moleculares em mulheres em transi??o menopausal e a influ?ncia do uso do ?cido lipoico (AL) nessas altera??es. O estudo do tipo duplo-cego, foi realizado com mulheres em perimenopausa submetidas ? um tratamento de 3 meses com 600 mg de AL administrados por via oral em duas doses di?rias, comparadas com um outro grupo que recebeu placebo durante o mesmo per?odo. O presente trabalho mostrou que as mulheres apresentaram uma circunfer?ncia de cintura (CC) e um ?ndice de massa corporal, em m?dia, acima dos valores preconizados pela OMS (CC &#8805; 80 cm; IMC > 25kg/m2). Al?m disso, essas mulheres apresentaram aumento nas concentra??es de colesterol total e triglicer?deos, al?m de valores de LDL pr?ximos do lim?trofe (Colesterol Total > 200mg/dL; Triglicer?deos > 150mg/dL; LDL >130mg/dL). Essas altera??es n?o sofreram influ?ncia do tratamento com AL. N?o foram encontradas altera??es no perfil hep?tico (ALT, AST e GGT) e renal (Ur?ia, Creatinina, Prote?nas Totais e Albumina) das mulheres ap?s o tratamento com AL, bem como no perfil mineral (C?lcio Total, C?lcio Ionizado, F?sforo e Magn?sio) e ?sseo (Osteocalcina, Fosfatase Alcalina Total e Fosfatase ?cida Tartarato Resistente). Os resultados do perfil oxidativo mostraram que o tratamento com AL diminuiu a atividade da enzim?tica da Glutationa Peroxidase (GPx) (p <0,01), enquanto para os par?metros Subst?ncias Reativas ao ?cido Tiobarbit?ricos (SRAT s), Glutationa Reduzida (GSH) e Super?xido Dismutase (SOD) n?o houve diferen?as. A SOD apesentou-se elevada no grupo placebo ap?s os 3 meses de estudo (p<0,05). A express?o do mRNA do RANKL em leuc?citos totais mostrou-se diminu?da (p < 0,05) e do RANK aumentada (p<0,001), ap?s o tratamento com AL, enquanto a express?o dos genes IL-6 e TNF-&#593; n?o apresentou altera??o. Podemos concluir que as mulheres em est?gio de perimenopausa, inicial de defici?ncia estrog?nica, apresentam altera??o no perfil lip?dico e composi??o corporal, e que essas altera??es poderiam estar induzindo altera??es no perfil oxidativo e do metabolismo ?sseo. Entretanto, o tratamento com AL se mostrou eficaz para o perfil oxidativo, bem como ?sseo j? que marcadores precoces como a atividade da GPx e a express?o do mRNA do RANKL, respectivamente, foram reduzidos associada a n?o altera??o na atividade da SOD. Estes resultados sugerem o efeito ben?fico e protetor do AL, indicando-o como uma alternativa para tratamento auxiliar nas complica??es associadas ? defici?ncia estrog?nica