The highly regulated maturation of the mammary gland is poorly understood. Our studies were designed to further characterize the role of ovarian hormones, growth hormone (GH)/IGF axis proteins and extracellular matrix (ECM) in the growth and development of prepubertal mammary glands. Prepubertal heifers were injected with either exogenous GH or subjected to ovariectomy (OVX). Mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested for DNA, protein, lipid, and western blot analysis. Remaining tissues were preserved for histological staining or snap frozen for quantitative real-time PCR. We examined 13 genes that work in conjunction with the extracellular matrix to regulate mammary proliferation and morphogenesis. Administration of GH, while impacting composition of MFP, had no effect on expression of the selected genes; there was a decrease in expression of fibronectin in PAR. Ovariectomy had no effect on gene expression in MFP but decreased expression of epimorphin, a potent regulator of morphogenesis, in PAR. In both experiments, the presence of a 55 kDa band corresponding to androgen converting enzyme aromatase was detected but its expression was unaffected. In another study, we used in vitro cell culture to evaluate the role of ECM in mammary gland maturation and employed quantitative real-time PCR to evaluate gene expression profiles of select genes involved in proliferation and differentiation. Expression of Rac1 was decreased in response to bovine insulin (BI) but increased on collagen I (Col). Expression of aldehyde dehydrogenase was decreased in BI and serum on plastic and on Col in the presence of BI. Expression of IGF binding proteins (BP) 3, -4, and -6 were decreased in the presence of serum on laminin (LM). Also, IGF-BP2 expression was decreased on Col while IGF-BP6 was increased on LM with BI. Clusterin, a ubiquitous non-adhesive ECM protein was not affected by ECM substrate but did increase over time. In conclusion, we propose that the mammary gland is not able to respond to GH at this age and that while OVX did effect the expression of some genes, the presence of aromatase maintained local estrogen concentrations. Furthermore, ECM alone is insufficient to regulate mammary gland development and growth. / Ph. D.

Objective - To evaluate a surgical technique for performing laparoscopic bilateral ovariectomy in standing horses. Study Design - Experimental study. Animals or Sample population - 8 mares, age 2-20 years, weight 410-540 kg. Methods - Standing laparoscopic bilateral ovariectomy was performed in 8 mares with normal anatomy of the reproductive tract. The Harmonic Scalpel (an ultrasonically activated instrument) was used to transect the ovarian pedicle and to obtain hemostasis simultaneously. Necropsy was performed on 4 mares 3 days after surgery and 30 days following surgery on the remaining 4 mares. Gross and histopathologic evaluation of the ovarian pedicles was performed to characterize the effects of the Harmonic Scalpel on the transected tissue. Results - The Harmonic Scalpel achieved complete hemostasis of the vasculature of the ovarian pedicles in all mares. Median transection time for the ovarian pedicle was 28 minutes. Postoperative complications included transient fever in one mare, moderate subcutaneous emphysema in another, and incisional seroma formation in a third mare. Post-mortem examination 3 and 30 days postoperatively revealed no signs of generalized peritonitis, postoperative hemorrhage or adhesion formation. Mild to moderate acute inflammation, and scar formation with moderate chronic inflammation at the ovarian pedicle was found 3 and 30 days after surgery, respectively. Median depth of coagulation necrosis 3 days postoperatively was 2.87 mm. Conclusions - The Harmonic Scalpel appears to provide reliable hemostasis of the ovarian pedicle during elective laparoscopic ovariectomy in horses. Clinical Relevance - The Harmonic Scalpel represents a safe alternative to other means of hemostasis during elective laparoscopic ovariectomy in horses. / Master of Science

A ovariectomia bilateral em ratas é um dos modelos experimentais utilizados para se analisar a menopausa e as possíveis estratégias para amenizar os efeitos deletérios desta condição. A suplementação da dieta com antioxidantes vem sendo utilizada para diminuir o risco de estresse oxidativo, que está aumentado na menopausa. Nesse estudo, foram analisados os efeitos do ácido lipoico (AL) e dos ômegas-3 (ácido docosahexaenóico (DHA) e ácido eicosapentaenóico (EPA)) no fígado, através da suplementação da dieta de ratas ovariectomizadas. O ácido lipoico foi escolhido em virtude da sua capacidade antioxidante, pela conhecida característica de ser cofator de enzimas chave no metabolismo celular e por inibir alguns mecanismos pró- inflamatórios. Essas características são importantes em virtude da disfunção mitocondrial e do aumento dos níveis de citocinas inflamatórias, que estão presentes após a menopausa. Os demais ácidos graxos poli-insaturados foram utilizados por possuírem alta capacidade antioxidante e estarem bem estabelecidos como protetores endoteliais. Além disso, também exercem efeitos anti-inflamatórios e são capazes de normalizar os níveis de lipídios na circulação sanguínea. Os resultados demonstram que o ácido lipoico é capaz de atuar no fígado e recuperar a atividade da enzima fumarase e a atividade das enzimas antioxidantes superóxido dismutase mitocondrial (MnSOD) e glutationa peroxidase (GPx), além de diminuir o dano oxidativo em proteínas e manter os níveis de malondialdeído (MDA) semelhantes ao grupo controle. No entanto, não exerceu influência na atividade da superóxido dismutase citosólica (CuZnSOD). A suplementação com DHA e EPA restaurou os níveis das duas classes de superóxidos dismutase, mas, não conseguiu restaurar a atividade da GPx e da fumarase. Os níveis de proteínas danificadas foram menores em todos os animais suplementados com ômega-3 em relação ao grupo controle e ao grupo ovariectomizado sem suplementação. Além disso, os suplementos também atuaram na redução dos níveis de nitritos e nitratos pois possuem propriedades anti-inflamatórias, sobretudo o ácido lipoico, que inibe a oxido nítrico sintase induzível (ONi) de macrófagos. Os níveis de vitamina C não apresentaram diferença entre os grupos SHAM, OVX, AL e DHA. Mas, o grupo EPA apresentou níveis de vitamina C inferiores aos dos grupos SHAM e OVX. Além disso, os níveis de vitamina E se mostraram inferiores nos grupos suplementados com os ácidos graxos poli-insaturados de cadeia longa. Neste trabalho, os antioxidantes assumiram um papel importante na diminuição do dano oxidativo e na recuperação da atividade de enzimas importantes na homeostase celular, alterações essas, causadas pela diminuição drástica dos níveis de estrogênio no modelo de menopausa. / The bilateral ovariectomy in rats is one of the experimental models used to analyze the menopause and possible strategies to mitigate the deleterious effects of this condition. Dietary supplementation with antioxidants has been used to decrease the risk of oxidative stress, which is increased in menopause. In this study, it was analyzed the effects of lipoic acid (LA) and the omega -3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) in the liver, through dietary supplementation of ovariectomized rats. The lipoic acid was chosen because of its antioxidant capacity, its known characteristic of being cofactor for key enzymes in cellular metabolism, and inhibition of some proinflammatory mechanisms. These characteristics are important because of mitochondrial dysfunction and increased levels of inflammatory cytokines, that are present after menopause. The other polyunsaturated fatty acids were used due to their high antioxidant capacity and well established endothelial protective role. Furthermore, they also exert anti-inflammatory effects and are able to normalize the lipid levels in the bloodstream. The results showed that lipoic acid is capable of acting in the liver and recover the activities of the fumarase enzyme and the antioxidant enzymes mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase (GPx), and reducing oxidative damage of proteins and maintaining the levels of malondialdehyde (MDA) similar to the control group. However, lipoic acid had no influence on the activity of cytosolic superoxide dismutase (CuZnSOD). Supplementation with DHA and EPA restored the levels of both classes of superoxide dismutase, but was unable to restore the activity of GPx and fumarase. The levels of damaged proteins were lower in all animals supplemented with omega -3 when compared to the sham and ovariectomized groups without supplementation. Also, the supplements were active in reducing levels of nitrites and nitrates, since they have anti -inflammatory properties, especially lipoic acid, which inhibits nitric oxide synthase inducible (iNOS) of macrophages. Vitamin C levels did not differ between the SHAM, LA, OVX and DHA groups. But the EPA group presented lower levels of vitamin C than those of SHAM and OVX groups. Nonetheless, levels of vitamin E was inferior in the groups supplemented with long chain polyunsaturated fatty acids. In this work, antioxidants played an important role in reducing oxidative damage and assists recovery of the activity of important enzymes in cellular homeostasis, changes caused by the drastic decrease in estrogen levels in menopausal model.

Made available in DSpace on 2014-06-11T19:30:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-10-23Bitstream added on 2014-06-13T20:01:17Z : No. of bitstreams: 1 alonso_jmsl_dr_sjc.pdf: 1064371 bytes, checksum: 4b5574d1963cb808bb8dd39cc9e27047 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Condições sistêmicas do hospedeiro podem modular a resposta inflamatória periodontal, determinando variação em relação à susceptibilidade individual e velocidade de progressão da doença periodontal. Dentre os fatores sistêmicos adquiridos, a osteoporose e o alcoolismo são descritos na literatura, como indicadores de risco para a perda óssea associada à doença periodontal. Este estudo objetivou analisar, para ratas Wistar, a influência do consumo crônico do etanol 20% associado à deficiência estrogênica considerando aspectos histológicos e histomorfométricos. Foram utilizadas sessenta ratas, com aproximadamente noventa dias, divididas em dois grupos correlacionados à cirurgia (OVZ) ou simulação cirúrgica de ovariectomia (SHAM). Cada grupo foi dividido em três subgrupos: (C) dieta controle, (A) dieta alcoólica 20% e (I) solução isocalórica ao etanol 20%. Após trinta dias da castração, iniciou-se a dieta e indução de periodontite experimental no primeiro molar inferior esquerdo, as quais foram mantidas por 56 dias. As regiões interproximais entre primeiro e segundo molar inferior esquerdo e o sítio contralateral sem indução da doença periodontal foram avaliadas quanto ao nível ósseo, perda de inserção e características inflamatórias. Os resultados demonstraram que em relação à significância para SHAMC e OVZ-C, a deficiência hormonal não foi capaz de induzir ou agravar a perda óssea na doença periodontal, mas acarretou alterações inflamatórias importantes. Considerando os grupos SHAM e OVZ e a ausência de doença periodontal, o etanol acarretou perda óssea e alterações inflamatórias para ambos os grupos, sendo observada maior severidade quando combinado à ovariectomia. Nas ratas com periodontite induzida, OVZ ou SHAM... / The immune system has an important paper in pathogenesis of the periodontal disease, being the host can modulate periodontal inflammatory reaction, determining variance to individual susceptibility and speed of progression of the periodontal disease. Amongst systemic acquired factors, osteoporosis and alcoholism are described in the literature, as risk indicators for bone loss associated with periodontal disease. The purpose of this study was evaluate histological and histomorfometrics aspects on influence of the chronic alcohol consumption in the ligature-induced periodontitis in rats with estrogen deficiency for. Sixty rats were used, with approximately 90 days-old, divided into two groups correlated surgery (OVZ) or surgical simulation of ovariectomy (SHAM). Each group was divided into three subgroups groups (C) control diet, (A) ethanol 20% containing liquid diet and (I) par-fed control diet. After thirty days of castration, diet and experimental periodontitis induction, which were maintained by 56 days. Interproximal regions between first and second molar lower left and the respective contralateral site without induction of periodontal disease were assessed as to the level osseous insertion loss and inflammatory characteristics. The results showed that in relation to the significance to SHAM-C and OVZ-C, hormone deficiency was not able to induce or aggravate the bone loss, but periodontitis has resulted in important inflammatory changes. Whereas the groups SHAM and OVZ and the absence of periodontitis, ethanol has resulted in bone loss and inflammatory changes to both groups, and also greater severity when combined with ovariectomy. In rats periodontitis induction, OVZ or SHAM, the 20% ethanol consumption doesn’t affect exacerbate bone... (Complete abstract click electronic access below)

Orientador: Wilter Ricardo Russiano Vicente / Coorientador: Maurício Veloso Brun / Banca: Giuliano Queiroz Mostachio / Banca: Maricy Apparício Ferreira / Banca: Leandro Zuccolotto Crivellenti / Resumo: Nos últimos anos a cirurgia minimamente invasiva vem ganhando cada vez mais adeptos por demonstrar vantagens inigualáveis em comparação à cirurgia convencional o que vem estimulando o desenvolvimento de instrumentais inovadores com potenciais aplicações na medicina veterinária. O presente estudo objetivou avaliar a técnica de portal único (SILSTM) para ovário-histerectomia videoassistida em cadelas, comparando-a à técnica laparoscópica videoassistida por "single-port" via endoscópio com canal de trabalho e com a técnica por celiotomia, verificando a curva de aprendizado, resposta inflamatória e comportamental, complicações trans-cirúrgicas e a perda sanguínea dos animais submetidos a estas técnicas. Foram avaliadas 30 fêmeas caninas, alocadas em três grupos com 10 animais em cada: ovário-histerectomia convencional por celiotomia (GI), ovário-histerectomia laparoscópica videoassistida por um único portal utilizando endoscópio com canal de trabalho (GII) e ovário-histerectomia laparoscópica com uso do dispositivo SILSTM (GIII). Foram avaliados os tempos cirúrgicos médios, numero de complicações trans e pós-cirúrgicas nos diferentes grupos, a intensidade da dor pós-operatória mediante aplicação da escalas de dor de Universidade de Melbourne, Glasgow e Morton e os níveis séricos da proteína C reativa e Interleucina-6 durante as primeiras 72 horas após o término dos procedimentos. A media de tempo obtidos foram de 30,20±6,41min para o grupo GI, 60,30±19,15 min para o grupo GII e 1... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Over the last few years, minimally invasive surgery is gaining more followers, by showing unparalleled advantages in front of conventional surgery. This fact has been stimulating the development of new instruments, potentially applicable on Veterinary Medicine. The current study aimed to evaluate the feasibility of a single portal technique (SILSTM) to ovariohysterectomy video assisted in bitches, comparing it to a video assisted technique by single-port using an endoscopy with work channel, and with celiotomy, assessing the learning curve, inflammatory and behavioral response, surgical complications and blood loss from animals subjected to these techniques. Thirty female dogs were evaluated, divided into 3 groups with 10 animals each (n=10): ovariohysterectomy by celiotomy (GI), laparoscopic ovariohysterectomy video assisted through a single-port using an endoscope with working channel (GII), and laparoscopic ovariohysterectomy using the SILSTM device (GIII). Mean surgical time, number of complications during and after surgery, pain level after surgery, and serum levels of C-reactive proteins (CRP) an Interleucin-6 (IL-6), were evaluated. Mean surgical times plus/minus standard deviations (SD) in minutes were 30.20±6.41, 60.30±19.15, and 119.42±32.78 for GI, GII and GIII, respectively. On GII, were noted three complications that didn't need to be converted to celiotomy and one that needs, while GIII presented three complications that needed to be converted to celiotomy. Rega... (Complete abstract click electronic access below) / Doutor

Osteoporosis affects the human skeleton through the direct effects of the disease on the function and structure of bone. Individuals who are affected by osteoporosis may be subject to serious fractures and it is estimated that annually approximately 1.5 million fractures can be attributed to this disease [1]. The disease is categorized as the direct side effect of increased bone porosity and bone loss and is directly linked to estrogen deprivation [2]. Animal models are often used to make initial conclusions about the effects of the disease or pharmacological treatments. In this study, sheep were chosen as a representative animal model due to their similar metabolic characteristics to that of a human. Like most animals, the ovine does not undergo a natural menopause and an ovariectomy was necessary to replicate the condition. The study objective was to quantify compact bone density present in ovine at three months post ovariectomy. The study included 112 ovine separated into different treatment groups. The treatment groups were separated into 4 groups of 28 based on season of surgery: autumn, winter, spring, and summer. Each seasonal group was further divided into 2 groups of 14; the first group underwent an ovariectomy; and the second group underwent a sham surgery, in which the ovaries were visualized and handled but left in the abdomen. One group was sacrificed 3 months post operatively and the other group was sacrificed at 12 months post operatively. This study specifically looks at ewe sacrificed at 3 months. The radius from each sheep was cut into the anatomical sectors: cranial, caudal, craniolateral, craniomedial, caudomedial, and caudolateral. Each anatomical sector was turned into a microradiograph for analysis. Densitometry was performed to determine the density of each specimen using the estimated thickness of aluminum (ETA) as the key. Statistical analysis assessed the resulting data to understand the effects of treatment, season of sacrifice, season of surgery, and anatomical sector by comparing both mean ETA and standard deviation ETA to understand changes in bone density. The results revealed significant differences between the ovariectomy and sham groups as well as variation within season of surgery and season of sacrifice in both groups. Anatomical sector showed no significant variation. The differences in the thickness of aluminum seen in the sheep that underwent a sham operation can be attributed to the presence of estrogen. The sheep that underwent an ovariectomy showed differences in the estimated thickness of aluminum that can be attributed to other seasonal characteristics including the influence of Vitamin D. The results and conclusions within this study can be used to influence bone material characteristics and bone loss test protocols in future osteoporosis and estrogen depletion studies.

Clinical and preclinical studies revealed that heart failure induces depression. Injury of myocardial tissue initiates an inflammation cascade that extends to the CNS and might contribute to depression following myocardial infarction (MI). Sex differences were noticed in the progression of heart failure and depression in clinical studies. We hypothesized that depression-like behavior induced by HF post-MI is influenced by sex through modulation of inflammation pathway. First, we evaluated sex differences in depression-like behavior in male and female rats at 8-10 weeks post-MI, as well as circulating cytokines, the extent of inflammation in the PFC, PVN, and amygdala, and mBDNF levels in the PFC and amygdala that are affected by neuroinflammation. Then we evaluated the effect of ovariectomy (OVX) and whether estrogen replacement with 17β-estradiol (E2) prevents post-MI induced depression-like behavior through inhibiting neuroinflammation. Thirdly we evaluated the role of inflammation for cardiac dysfunction and development of depression-like behavior in OVX female rats post-MI by oral treatment with pentoxifylline (PTX). Male rats developed depression-like behavior by ten weeks post-MI but not females as assessed by sucrose preference test (SPT) and forced swim test (FST). Both developed similar cardiac dysfunction and a comparable increase in plasma and PVN cytokine levels, but cytokine levels increased and mBDNF levels decreased only in the PFC of male rats post-MI. OVX per se decreased sucrose consumption and induced passive behavior assessed by SPT and FST, respectively.The combination of MI and OVX aggravated depression-like behvaiour. E2 treatment prevented the development of mild depression-like behavior in OVX and severe symptoms in OVX female rats post-MI. E2 had no effect on cardiac dysfunction in OVX female rats at 10 weeks post-MI. Despite the similar increase in circulating cytokines in OVX ± E2 at 10 weeks post-MI, E2 decreased the proinflammatory cytokines and increased IL-10 (anti-inflammatory cytokine) in the PFC. Finally, we evaluated the role of neuroinflammation in depression-like behavior in OVX female rats post-MI through inhibiting cytokine production by administering oral PTX. PTX prevented depression-like behavior in OVX female rats post-MI and reduced cytokines levels in plasma, PVN and PFC. However, PTX did not affect the progression of cardiac dysfunction at 10 weeks post-MI. Sex determines the development of depression-like behavior in HF post-MI and neuroinflammation appears to play a critical pathway that is affected by sex and can be inhibited by hormonal replacement or anti-inflammatory agents.

Breast cancer is the most common malignancy affecting women and the second leading cause of death among women in the United States. Alcohol consumption is one of the few modifiable risk factors for breast cancer development but the mechanism by which it contributes to mammary cancer development and progression remains unclear, although it has been suggested that estrogen is critical for this process. To determine if alcohol promotes mammary tumor development via the estrogen pathway, estrogen receptor alpha-negative (ER[alpha]-negative) MMTV-neu mice were treated with various doses of ethanol and activation of estrogen signaling was measured. Our results showed that alcohol consumption increased estrogen signaling activation, serum estrogen levels and, most interestingly, expression of ER[alpha] in tumor tissue in the ER[alpha]-negative mice. Several lines of evidence in literature suggest that ER[alpha] expression in ER[alpha]-negative cancer cells is inhibited through epigenetic regulation. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than DNA sequence changes. Thus, to determine whether alcohol may regulate ER[alpha] re-expression in ER[alpha]-negative breast cancer cells through epigenetic mechanisms, we examined the effects of ethanol on CpG methylation and histone modifications (acetylation and methylation) of two ER[alpha]-negative breast cancer cell lines, MDA-MB-231 (human) and MMTV-neu (mouse). We also examined whether the epigenetic modifications subsequently affect the recruitment of transcriptional regulation complexes to the ER[alpha] promoter to regulate ER[alpha] transcription. Results showed that alcohol promotes ER[alpha] re-expression in these ER[alpha]-negative cell lines and that this effect was associated with decreased CpG methylation, an overall increase of histone acetylation and decrease of histone methylation, and an alteration in the enrichment of the ER[alpha] transcriptional regulation complexes (pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1) at the ER[alpha] promoter, which may contribute to cancer cell progression. In addition, we found that the inhibition of ER[alpha] by tamoxifen specifically blocks the effects of alcohol on ER[alpha] reactivation. To determine how alcohol promotes cell invasive ability, a critical process for cancer progression, we examined the role of two genes, metastasis suppressor Nm23 and integrin alpha-5 ITGA5, which we identified to be important for alcohol-induced breast cancer cell invasion. It has previously been shown that estrogen may regulate Nm23 expression and that estrogen regulation may be important for ITGA5-mediated cancer progression. Our results showed that alcohol promotes cancer cell invasion through the down-regulation of Nm23, which led to the subsequent increase of ITGA5 and increase of cell invasion. Collectively, data from my research strongly supports and provides evidence that alcohol promotes breast cancer development and progression through the regulation of estrogen signaling. / text

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

A ovariectomia bilateral em ratas é um dos modelos experimentais utilizados para se analisar a menopausa e as possíveis estratégias para amenizar os efeitos deletérios desta condição. A suplementação da dieta com antioxidantes vem sendo utilizada para diminuir o risco de estresse oxidativo, que está aumentado na menopausa. Nesse estudo, foram analisados os efeitos do ácido lipoico (AL) e dos ômegas-3 (ácido docosahexaenóico (DHA) e ácido eicosapentaenóico (EPA)) no fígado, através da suplementação da dieta de ratas ovariectomizadas. O ácido lipoico foi escolhido em virtude da sua capacidade antioxidante, pela conhecida característica de ser cofator de enzimas chave no metabolismo celular e por inibir alguns mecanismos pró- inflamatórios. Essas características são importantes em virtude da disfunção mitocondrial e do aumento dos níveis de citocinas inflamatórias, que estão presentes após a menopausa. Os demais ácidos graxos poli-insaturados foram utilizados por possuírem alta capacidade antioxidante e estarem bem estabelecidos como protetores endoteliais. Além disso, também exercem efeitos anti-inflamatórios e são capazes de normalizar os níveis de lipídios na circulação sanguínea. Os resultados demonstram que o ácido lipoico é capaz de atuar no fígado e recuperar a atividade da enzima fumarase e a atividade das enzimas antioxidantes superóxido dismutase mitocondrial (MnSOD) e glutationa peroxidase (GPx), além de diminuir o dano oxidativo em proteínas e manter os níveis de malondialdeído (MDA) semelhantes ao grupo controle. No entanto, não exerceu influência na atividade da superóxido dismutase citosólica (CuZnSOD). A suplementação com DHA e EPA restaurou os níveis das duas classes de superóxidos dismutase, mas, não conseguiu restaurar a atividade da GPx e da fumarase. Os níveis de proteínas danificadas foram menores em todos os animais suplementados com ômega-3 em relação ao grupo controle e ao grupo ovariectomizado sem suplementação. Além disso, os suplementos também atuaram na redução dos níveis de nitritos e nitratos pois possuem propriedades anti-inflamatórias, sobretudo o ácido lipoico, que inibe a oxido nítrico sintase induzível (ONi) de macrófagos. Os níveis de vitamina C não apresentaram diferença entre os grupos SHAM, OVX, AL e DHA. Mas, o grupo EPA apresentou níveis de vitamina C inferiores aos dos grupos SHAM e OVX. Além disso, os níveis de vitamina E se mostraram inferiores nos grupos suplementados com os ácidos graxos poli-insaturados de cadeia longa. Neste trabalho, os antioxidantes assumiram um papel importante na diminuição do dano oxidativo e na recuperação da atividade de enzimas importantes na homeostase celular, alterações essas, causadas pela diminuição drástica dos níveis de estrogênio no modelo de menopausa. / The bilateral ovariectomy in rats is one of the experimental models used to analyze the menopause and possible strategies to mitigate the deleterious effects of this condition. Dietary supplementation with antioxidants has been used to decrease the risk of oxidative stress, which is increased in menopause. In this study, it was analyzed the effects of lipoic acid (LA) and the omega -3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) in the liver, through dietary supplementation of ovariectomized rats. The lipoic acid was chosen because of its antioxidant capacity, its known characteristic of being cofactor for key enzymes in cellular metabolism, and inhibition of some proinflammatory mechanisms. These characteristics are important because of mitochondrial dysfunction and increased levels of inflammatory cytokines, that are present after menopause. The other polyunsaturated fatty acids were used due to their high antioxidant capacity and well established endothelial protective role. Furthermore, they also exert anti-inflammatory effects and are able to normalize the lipid levels in the bloodstream. The results showed that lipoic acid is capable of acting in the liver and recover the activities of the fumarase enzyme and the antioxidant enzymes mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase (GPx), and reducing oxidative damage of proteins and maintaining the levels of malondialdehyde (MDA) similar to the control group. However, lipoic acid had no influence on the activity of cytosolic superoxide dismutase (CuZnSOD). Supplementation with DHA and EPA restored the levels of both classes of superoxide dismutase, but was unable to restore the activity of GPx and fumarase. The levels of damaged proteins were lower in all animals supplemented with omega -3 when compared to the sham and ovariectomized groups without supplementation. Also, the supplements were active in reducing levels of nitrites and nitrates, since they have anti -inflammatory properties, especially lipoic acid, which inhibits nitric oxide synthase inducible (iNOS) of macrophages. Vitamin C levels did not differ between the SHAM, LA, OVX and DHA groups. But the EPA group presented lower levels of vitamin C than those of SHAM and OVX groups. Nonetheless, levels of vitamin E was inferior in the groups supplemented with long chain polyunsaturated fatty acids. In this work, antioxidants played an important role in reducing oxidative damage and assists recovery of the activity of important enzymes in cellular homeostasis, changes caused by the drastic decrease in estrogen levels in menopausal model.