α-Lipoic acid (LA) has been shown to improve the diabetic cardiac symptoms. However, the underlying mechanisms have not been elucidated precisely. We have reported recently that LA potentially protected neurons from substance-induced apoptosis. We hypothesized that LA could attenuate cardiac cells death induced by oxidative stress derived from high glucose. To test this possibility, we examined the effects of LA on . d-glucose/glucose oxidase (DG/GO, 30. mM/5. mU)-induced injury in rat cardiomyoblast H9c2 cells. We observed that LA pretreatment significantly increased cell viability in DG/GO-challenged cells. LA pretreatment also attenuated DG/GO-induced apoptosis as evidenced by decreases in both nuclear condensation and loss of mitochondrial potential. In addition, LA activated ERK1/2 and moderately increased ROS production. Blockade of ERK1/2 activation by PD98059 completely abolished LA-induced protection against DG/GO challenge. Inhibition of ROS by . N-acetylcysteine abrogated LA-induced ERK1/2 activation and cytoprotection. Furthermore, we observed that the ROS production induced by LA was significantly slower and milder than that by DG/GO. Our results suggest that pretreatment with LA moderately increased ROS production to induce a preconditioning-like effect by ERK1/2 activation thereby increased tolerance of H9c2 cells to DG/GO challenge.

Background: Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth. Methods: To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for α-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth. Results: LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth. Conclusion: Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Background: Bupivacaine is an amide type local anesthetic which is widely used for epidural anesthesia and nerve blockade in patients. However, local administration of bupivacaine could cause neuron injury showing transient neurologic symptoms. α-Lipoic acid (LA) was shown to protect nerve cells from substance-induced injury. We hypothesized that LA administration could attenuate bupivacaine-induced neurotoxicity. Methods: To evaluate our hypothesis, we treated mouse neuroblastoma N2a cells with LA 30 min before the cells were exposed to bupivacaine. We evaluated cellular injury by examination of cell viability, morphology changes, nuclear condensation, and Annexin V staining. We also examined the levels of intracellular reactive oxygen species (ROS) and activation of PI3K/Akt signaling pathway. In a separate experiment, we determined the effect of Akt inhibition on cell viability in the presence of LA and bupivacaine. Results: Bupivacaine treatment significantly induced cell injury as evidenced by decreased cell viability, increased nuclear condensation and Annexin V staining. Administration of LA significantly attenuated bupivacaine-induced cell injury. In addition, LA treatment increased the levels of phospho-Akt and phospho-GSK3β and attenuated bupivacaine decreased the levels of ROS. More significantly, pharmacological inhibition of Akt abolished the LA-induced protection from bupivacaine-caused cell injury. Conclusions: Our findings suggest that pretreatment of neuroblastoma cells with LA protected neural cells from bupivacaine-induced injury. The mechanisms involve activation of the PI3K/Akt signaling pathway.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第24638号 / 工博第5144号 / 新制||工||1982(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 跡見 晴幸, 教授 森 泰生, 教授 浜地 格 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

One of the matchless ironies of the human body is its requirement for the highly reactive oxygen molecule, which has been clearly implicated in many diseases and the aging processes. Oxidants produced by metabolic processes damage cells by starting chemical chain reactions including oxidation of DNA and proteins as well as lipid peroxidation. Damage to DNA can cause mutations and lead to cancer if not reversed by DNA repair mechanisms. Damage to proteins causes enzyme inhibition, denaturation and protein degradation. Lipid peroxidation can cause cell lysis as well as creating mutagenic and carcinogenic by-products. The human body contains antioxidants and enzymes that together work to prevent oxidative damage to cellular components. By and large antioxidants either prevent these reactive oxygen species from being formed or remove them before they cause damage. There are many theories currently that tout the superior nature of diverse antioxidant combinations. One such theory is by Dr. Lester Packer of The University of California at Berkley. Dr. Packer puts forth the hypothesis that there is a superlative combination of five antioxidants that have the ability to "recharge" one another both in the blood plasma and intracellularly. This would result in a greater quality of antioxidant protection for an extended time. The current study evaluates Dr. Packer's theory of antioxidant combination from his book The Antioxidant Miracle. The decay rate of the antioxidants vitamin E, vitamin C, lipoic acid, glutathione, and coenzyme Q10 alone and in combination were determined using the ORAC (Oxygen Radical Absorbance Capacity) assay. The majority of the antioxidants retained activity for longer periods of time when tested alone, rather than in combination as Dr. Packer's theory would suggest. The assay was also preformed (using the same antioxidants and combinations) on oxidatively damaged Raji cancer cells. Cell viability and uptake of antioxidants into the cytoplasm were monitored. Finally, a variety of multivitamins were subjected to the ORAC assay and their antioxidant capacity compared to that of the "Packer Combination". The results suggest that multivitamins are superior antioxidants than the Packer ratio listed in The Antioxidant Miracle.

A síndrome de ardência bucal (SAB) é uma condição crônica, caracterizada por sensação de ardor bucal sem alterações clinicamente detectáveis. Afeta predominantemente mulheres no período pós-menopausa e sua terapêutica ainda não está estabelecida. Pelo menos dois terços destes pacientes apresentam queixa subjetiva de disgeusia como sintoma secundário associado. O objetivo deste estudo foi avaliar a efetividade do ácido alfa lipóico, como alternativa terapêutica no controle dos sintomas da SAB, por meio de um estudo duplo-cego cruzado, placebocontrolado. Foi realizada também uma investigação da função gustatória destes pacientes, pela aplicação de teste objetivo de reconhecimento dos quatro sabores básicos. Foram incluídos trinta e cinco pacientes (31 mulheres, 4 homens, média de idade 63,1 anos, variação 36-78 anos) e 31 pacientes completaram o estudo terapêutico. Os pacientes foram randomizados para dois ciclos de tratamento um com ácido alfa lipóico e um com placebo, ambos administrados em cápsulas idênticas. Estes ciclos de tratamento foram separados por um período de washout de 20 dias. O sintoma de ardor bucal e a resposta terapêutica foram avaliadas utilizando uma escala visual de sintomatologia (EVS) numérica de 10 pontos antes do início e ao término de cada ciclo e pelo efeito global percebido (EGP), usando uma escala de 5 pontos ao término de cada ciclo de tratamento. O nível de redução sobre o sintoma de ardor avaliado pela EVS foi estatisticamente significante para ambos os tratamentos (31,15% com ácido alfa lipoico e 34,09% ao término do do primeiro ciclo; 12,55% para ácido alfa lipóico e 28,09% para placebo ao término do segundo ciclo). Considerando-se os resultados de EGP dos dois ciclos, 22 pacientes reportaram pelo menos alguma melhora após utilizarem ácido alfa lipóico e 23 pacientes após utilizarem placebo. A comparação dos scores obtidos dos dois ciclos pelo teste t falharam em demonstrar efetividade para ácido alfa lipóico sobre placebo. A queixa subjetiva de disgeusia esteve associada à de ardor em 60% dos casos. No teste objetivo de paladar foram verificados erros de identificação dos sabores básicos em 35,23% das amostras para o amargo, 20% para o azedo, 20% para o doce e 19% para salgado, estes erros foram observados também entre pacientes que não apresentavam a queixa subjetiva de disgeusia. Apenas 5 pacientes (14,28%) conseguiram identificar corretamente os quatro sabores básicos. A maior parte dos erros de identificação ocorreu para o sabor amargo e em baixas concentrações. A análise dos dados obtidos nos permitiu concluir que o ácido alfa lipóico não foi efetivo no controle dos sintomas associados à síndrome de ardência bucal e que existe uma associação da síndrome com as alterações da função gustatória. / The burning mouth syndrome is a chronic condition caractherized by an oral burning sensation without clinical signs. Post menopausean women are mostly affected and the therapy is not stablished. Two thirds or more of these patients shown dysgeusia as a secondary associate complaint. The purpose of this study was to evaluate the effectiveness of alpha lipoic acid in the management of burning mouth syndrome symptoms through a randomized double-blind placebo-controlled crossover trial. In addiction, a preliminary evaluation of taste function was performed by objective test to recognition of the four basic flavors. Thirty-five patients (31 women, 4 men, median age 63.1 years, range 36-78) were included and 31 completed the therapeutic study. The patients were randomized for two cycles of treatmentone with alpha lipoic acid and one with placebo, both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 10 point numerical visual analogue scale (VAS) before and after each cycle and the global perceived effect (GPE) score, using a 5- point scale at the end of each treatment cycle. The level of burning reduction assessed by VAS was significant for both treatments (31.15% with ALA treatment and 34.09% with placebo after first cycle and 12.55% for ALA and 28.09% for placebo after second cycle). Considering the results of GPE in the two cycles together, twenty-two patients reported at least some improvement after alpha lipoic acid use and twenty-three patients after placebo. Comparison of the oral assessment scores of the two cycles with t test failed to demonstrate effectiveness for alpha lipoic acid over placebo. Dysgeusia was associated with burning mouth in 60% of the cases. In the objective taste evaluation, identification errors were observed in 35,23% of the samples for bitter, 20% for sour, 20% for sweet and 19% for salty. Moreover, these errors were observed among patients whose not complain of dysgeusia. Only 5 patients (14,28%) had correct identification of four basic flavors. Most of identifications errors were observed in bitter taste and in lower concentrations. We concluded that alpha lipoic acid was not effective in the control of burning mouth syndrome symptoms in this study and there is a relation of taste disfunction with the syndrome.

A menopausa é identificada como uma fase onde é desencadeada uma série de distúrbios fisiológicos e metabólicos devido à queda brusca dos hormônios sexuais, que desempenham funções importantes como o controle dos ciclos ovulatórios e antioxidantes naturais. Com o hipoestrogenismo ocorre uma variedade de desordens que vão desde aumento de peso e mudanças no humor até doenças cardiovasculares e neurodegenerativas. Muitas destas doenças estão relacionadas com o estresse oxidativo. A reposição hormonal com estrogênio vem sendo repensada devido seus possíveis efeitos colaterais. A suplementação com antioxidantes de fontes variadas é uma alternativa para amenizar os sintomas da menopausa, melhorando assim a qualidade de vida das mulheres que se encontram nesta fase. Este estudo teve por finalidade avaliar a resposta do estresse oxidativo no coração de ratas Wistar ovariectomizadas, após suplementação com ácidos graxos (AG) eicosapentaenóico (EPA) e docosahexaenóico (DHA), provenientes do ômega-3 e o ácido lipoico (AL), em um período de 3 meses. Foram realizadas as análises de biomarcadores, quantificando antioxidantes enzimáticos e não enzimáticos, bem como marcadores de danos em lipídeos e proteínas com a quantificação de Malondialdeído (MDA) e identificação de grupos carbolinados, respectivamente. Como resultados deste estudo, a ovarectomia gerou alterações no perfil oxidativo das ratas. A suplementação com EPA, DHA e AL demonstrou a recuperação dos níveis normais de consumo de H2O2 (catalase, peroxirredoxinas), da atividade de glutationa S-transferase (GST), superóxido dismutase (SOD) e glutationa total (GSHt) nas ratas tratadas. A atividade da glutationa peroxidase (GPx) retornou aos níveis normais com a suplementação com DHA. Já o tratamento com EPA foi mais efetivo para o aumento da Vit E, quando comparado ao grupo controle. Os danos em proteínas foram menores em todos os grupos suplementados. Os danos em lipídios foram menores no grupo tratado com AL, quando comparados ao grupo SHAM (grupo controle).Os resultados sugerem um efeito protetor do ácido lipoico e do ômega-3 no coração de ratas ovariectomizadas em relação ao dano oxidativo. / Menopause is identified as a phase where triggers a series of physiological and metabolic disorders due to the sharp drop of sex hormones, which play important functions like controlling the ovulatory cycles and natural antioxidants. With hypoestrogenism occurs a variety of disorders ranging from weight gain and changes in the mood to cardiovascular and neurodegenerative diseases. Many of these diseases are associated with oxidative stress. Hormone replacement with estrogen is being rethought because of their possible side effects. Supplementation with antioxidants from different sources is an alternative to alleviate menopausal symptoms, thus improving the quality of life of women who are at this stage. This study aimed to evaluate the response of oxidative stress in the heart of Wistar ovariectomized rats, after supplementation with fatty acids (FA) eicosapentaenoic (EPA) and docosahexaenoic acid DHA), derived from omega-3 and lipoic acid (LA), in a 3 month period. The biomarker analyzes were performed by quantifying enzymatic and non-enzymatic antioxidants and damage markers in lipids and proteins with the quantification of Malondialdehyde (MDA) and identifying carbonylated groups, respectively. As a result of this study, ovariectomy generated changes in oxidative profile of rats. The supplementation with EPA, DHA and LA showed recovery of normal levels of H2O2 consumption (catalase peroxiredoxins), glutathione activity S-transferase (GST), superoxide dismutase (SOD), and total glutathione (GSHt) in treated rats. The activity of glutathione peroxidase (GPx) returned to normal levels with supplementation with DHA. Since treatment with EPA was more effective for increasing vitamin E compared to the control group. Protein damage were lower in all supplemented groups. The damage in lipids were lower in the group treated with LA when compared to SHAM group (group control). The results suggest a protective effect of lipoic acid and omega-3 in the heart of ovariectomized rats compared to oxidative damage.

Increased oxidative stress and impaired antioxidant defense mechanisms are believed to be the important factors contributing to the pathogenesis and progression of diabetes mellitus. The products of lipid peroxidation and protein oxidation reactions were all found to be elevated significantly (p&lt / 0.05) in diabetic animals and supplementing the animals either individually or in combination, with two powerful antioxidants DL-&amp / #945 / -lipoic acid (LA) and vitamin C (VC) brought this increment toward the control values. Considering Cu-Zn SOD, CAT and GST-Mu, there was a significant decrease in all activities in diabetic group as compared with control animals. RT-PCR and Western blot analysis results demonstrated that this decrease in activity is regulated at the level of gene expression, as both mRNA and protein expressions were also suppressed for these enzymes. However, in diabetic animals both the mRNA expressions and the activities of two other antioxidant enzymes, namely Mn SOD and GPx, did not change, indicating that the control of activities of these two enzymes were not at the level of genes. Supplementing the diabetic animals with VC increased all CAT, Cu-Zn SOD, GPx, and GST-Mu activities without changing both mRNA and protein expressions suggesting the possible role of post-translational modifications. On the other hand, the effect of VC on Mn SOD was observed at mRNA levels reflecting a transcriptional regulation. Furthermore, supplementing the animals with LA increased the CAT, Cu-Zn SOD, Mn SOD and GPx activities in diabetic rats but different from VC, LA also increased mRNA of CAT and protein levels of CAT, Cu-Zn SOD and Mn SOD suggesting both transcriptional and translational regulation showed by LA. Combined application of antioxidants also increased the CAT, Cu-Zn SOD, Mn SOD and GPx activities toward the control values, but this time there were no statistically significant change in their mRNA expressions even though protein amounts of both CAT and GPx were augmented. That is, when given together, these antioxidants exert their effects mainly at the level of protein synthesis. As a conclusion, diabetes and the resulting oxidative stress coordinately regulate the activities of the antioxidant enzymes at different regulatory points. LA and VC, two powerful antioxidants affect all antioxidant enzyme activities at different levels of transcription and translation. The results indicated the presence of very intricate control mechanisms regulating the activities of antioxidant enzymes in order to prevent the damaging effects of oxidative stress.

A menopausa é identificada como uma fase onde é desencadeada uma série de distúrbios fisiológicos e metabólicos devido à queda brusca dos hormônios sexuais, que desempenham funções importantes como o controle dos ciclos ovulatórios e antioxidantes naturais. Com o hipoestrogenismo ocorre uma variedade de desordens que vão desde aumento de peso e mudanças no humor até doenças cardiovasculares e neurodegenerativas. Muitas destas doenças estão relacionadas com o estresse oxidativo. A reposição hormonal com estrogênio vem sendo repensada devido seus possíveis efeitos colaterais. A suplementação com antioxidantes de fontes variadas é uma alternativa para amenizar os sintomas da menopausa, melhorando assim a qualidade de vida das mulheres que se encontram nesta fase. Este estudo teve por finalidade avaliar a resposta do estresse oxidativo no coração de ratas Wistar ovariectomizadas, após suplementação com ácidos graxos (AG) eicosapentaenóico (EPA) e docosahexaenóico (DHA), provenientes do ômega-3 e o ácido lipoico (AL), em um período de 3 meses. Foram realizadas as análises de biomarcadores, quantificando antioxidantes enzimáticos e não enzimáticos, bem como marcadores de danos em lipídeos e proteínas com a quantificação de Malondialdeído (MDA) e identificação de grupos carbolinados, respectivamente. Como resultados deste estudo, a ovarectomia gerou alterações no perfil oxidativo das ratas. A suplementação com EPA, DHA e AL demonstrou a recuperação dos níveis normais de consumo de H2O2 (catalase, peroxirredoxinas), da atividade de glutationa S-transferase (GST), superóxido dismutase (SOD) e glutationa total (GSHt) nas ratas tratadas. A atividade da glutationa peroxidase (GPx) retornou aos níveis normais com a suplementação com DHA. Já o tratamento com EPA foi mais efetivo para o aumento da Vit E, quando comparado ao grupo controle. Os danos em proteínas foram menores em todos os grupos suplementados. Os danos em lipídios foram menores no grupo tratado com AL, quando comparados ao grupo SHAM (grupo controle).Os resultados sugerem um efeito protetor do ácido lipoico e do ômega-3 no coração de ratas ovariectomizadas em relação ao dano oxidativo. / Menopause is identified as a phase where triggers a series of physiological and metabolic disorders due to the sharp drop of sex hormones, which play important functions like controlling the ovulatory cycles and natural antioxidants. With hypoestrogenism occurs a variety of disorders ranging from weight gain and changes in the mood to cardiovascular and neurodegenerative diseases. Many of these diseases are associated with oxidative stress. Hormone replacement with estrogen is being rethought because of their possible side effects. Supplementation with antioxidants from different sources is an alternative to alleviate menopausal symptoms, thus improving the quality of life of women who are at this stage. This study aimed to evaluate the response of oxidative stress in the heart of Wistar ovariectomized rats, after supplementation with fatty acids (FA) eicosapentaenoic (EPA) and docosahexaenoic acid DHA), derived from omega-3 and lipoic acid (LA), in a 3 month period. The biomarker analyzes were performed by quantifying enzymatic and non-enzymatic antioxidants and damage markers in lipids and proteins with the quantification of Malondialdehyde (MDA) and identifying carbonylated groups, respectively. As a result of this study, ovariectomy generated changes in oxidative profile of rats. The supplementation with EPA, DHA and LA showed recovery of normal levels of H2O2 consumption (catalase peroxiredoxins), glutathione activity S-transferase (GST), superoxide dismutase (SOD), and total glutathione (GSHt) in treated rats. The activity of glutathione peroxidase (GPx) returned to normal levels with supplementation with DHA. Since treatment with EPA was more effective for increasing vitamin E compared to the control group. Protein damage were lower in all supplemented groups. The damage in lipids were lower in the group treated with LA when compared to SHAM group (group control). The results suggest a protective effect of lipoic acid and omega-3 in the heart of ovariectomized rats compared to oxidative damage.

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