Le rôle de l'inflammation dans le développement et la progression des maladies rénales chroniques (MRC) chez le chat a été peu étudié. L'hepcidine est une protéine de la phase aigue (PPA) de l'inflammation qui contribue au développement des anémies lors de MRC chez l'homme. Les objectifs de cette étude sont de comparer les concentrations en PPAs, en erythropoietine (EPO) ainsi que le statut en fer entre un groupe de chats sains et en MRC. 18 chats sains et 38 chats en MRC ont été recrutés de façon prospective. Les examens réalisés incluaient hématologie, biochimie, analyse d'urine, Serum amyloid A (SAA), haptoglobine (HAP), EPO, hepcidine,fer, TIBC et ferritinne. Nous avons observé une augmentation significative des concentrations en SAA et en hepcidine ainsi qu'une diminution significative du fer et du TIBC dans le groupe MRC (P < .05). Une corrélation positive entre la créatinine et certaines PPAs (SAA and hepcidin; P < .05) était présente. L'augmentation de SAA et hepcidine était significativement associé avec une diminution du TIBC et de l'hématocrite dans le groupe MRC. Les 14 (37%) chats anémiques du groupe MRC avaient une concentration significativement plus basse en fer et en TIBC (P < .05), changements compatibles avec une déficience fonctionelle en fer. Aucun chat n'avait un panel de fer compatible avec une carence en fer absolue. En conclusion, les résultats de cette étude suggèrent que les MRC chez le chat sont des conditions pro-inflammatoires, ayant un impact sur le métabolisme du fer. / The role of inflammation in the development and progression of feline chronic kidney disease (CKD) is not well characterized. Hepcidin, a recently discovered acute phase protein (APP) contributes to the development of anemia in human patients with CKD. The objectives of our study was to compare plasma APP including hepcidin, iron status, and erythropoietin (EPO) concentrations between healthy and cats with naturally occurring CKD. Eighteen healthy control cats and 38 cats with CKD were prospectively recruited. Complete physical examination along with hematology, biochemistry, plasma amyloid A (SAA), haptoglobine (HAP), EPO, iron, TIBC and ferritin were performed using routine laboratory analyses and commercially available feline ELISA-assays. Hepcidin-25 concentration was assessed with a human ELISA kit (DRG® Diagnostics). We found that mean SAA and hepcidin concentration were significantly higher and mean total iron and TIBC were significantly lower in the CKD group (P < .05). There was a significant positive correlation between creatinine and APPs (SAA and hepcidin; P < .05). Increase in SAA and hepcidin was also significantly associated with decrease of TIBC and PCV in the CKD group. The 14 (37%) anaemic cats with CKD had significantly and lower iron, TIBC, consistent with functional iron deficiency (P < .05). There were no patients with an iron profile suggestive of a true iron deficiency. There was no association with survival. In conclusion, our data suggest that feline CKD is a pro-inflammatory state, having significant impact on iron metabolism. With further validation, hepcidin may help better characterize these interactions.

Submitted by admin tede (tede@pucgoias.edu.br) on 2017-04-27T14:46:13Z No. of bitstreams: 1 JÉSSICA BARLETTO DE SOUSA BARROS.pdf: 1338303 bytes, checksum: f224cbe0cdd0f2bfa58ecbb4e530e87a (MD5) / Made available in DSpace on 2017-04-27T14:46:13Z (GMT). No. of bitstreams: 1 JÉSSICA BARLETTO DE SOUSA BARROS.pdf: 1338303 bytes, checksum: f224cbe0cdd0f2bfa58ecbb4e530e87a (MD5) Previous issue date: 2017-03-16 / The Zika virus (ZIKV) is a Flavivirus belonging to the family Flaviviridae, which was initially found and isolated on a Rhesus monkey in the Zika forest, Africa, in 1947. It is responsible for causing Zika fever, characterized mainly by symptoms such as fever, headache, Arthralgia, myalgia, and maculopapular rash. Currently, ZIKV infection has been considered an emerging and endemic infection and therefore several clinical aspects of the disease have been clarified, but there are still inflammatory features that need to be elucidated. The aim of the present study was to evaluate the inflammatory cytokines (IL-1β, IL-2, IL-5, IL-6, IL-7, IL-9, IL-12p70, IL-15 and IL-17A), anti-inflammatory (IL-4, IL-10, IL-13 and IL-1ra), and acute phase proteins (C-reactive protein and ferritin) in ZIKV-infected patients. We observed alterations in levels of C-reactive protein in ZIKV-infected patients when compared to healthy donors, and it was verified in the acute and convalescent phase. In relation to ferritin levels, they did not present significant changes at any point in the study. An increase in IL-5, IL-7 and IL-9 was also observed when compared to the acute and control groups. No changes were found in IL-4, IL-10 and IL-13 cytokines, however significant levels of IL-1ra were detected in ZIKV-infected individuals. Regarding the acute and convalescent phase, only IL-7 presented statistically significant values. All these molecules were correlated with the amount of signs and symptoms, and no statistical difference was observed. / O Zika vírus (ZIKV) é um Flavivírus pertencente à família Flaviviridae, que foi inicialmente encontrado e isolado em um macaco Rhesus na floresta Zika, África, em 1947. É responsável por ocasionar a febre Zika, caracterizada principalmente por sintomas como febre, cefaleia, artralgia, mialgia e exantema maculopapular. Atualmente, a infecção pelo ZIKV têm sido considerada uma infecção emergente e endêmica e por isso diversos aspectos clínicos da doença já foram esclarecidos, mas ainda existem características inflamatórias que precisam ser elucidadas. Assim, o presente trabalho objetivou avaliar as citocinas inflamatórias (IL-1β, IL-2, IL-5, IL-6, IL-7, IL-9, IL-12p70, IL-15 e IL-17A), anti-inflamatórias (IL- 4, IL-10, IL- 13 e IL-1ra), e proteínas de fase aguda (proteína C reativa e ferritina) em infectados pelo ZIKV. Observamos alterações nos níveis da Proteína C Reativa em infectados pelo ZIKV quando comparados aos doadores saudáveis, o mesmo foi verificado na fase aguda e convalescente. Em relação aos níveis de ferritina, esses não apresentaram alterações consideráveis em nenhum momento do estudo. Também foi constatado um aumento da IL-5, IL-7 e IL-9, quando comparado os níveis da fase aguda e grupo controle. Não foram encontradas alterações nos níveis das citocinas IL-4, IL-10 e IL-13, no entanto níveis significativos de IL-1ra foram detectados em infectados pelo ZIKV. Em relação a fase aguda e convalescente, apenas a IL-7 apresentou valores significativamente estatísticos. Todas essas moléculas foram correlacionadas com a quantidade de sinais e sintomas, e nenhuma diferença estatística foi observada.

The Gram-negative bacterium Photorhabdus luminescens is a pathogen of insects. It is able to secrete a variety of toxins and effectors against its host in order to escape its immune defences. The model insect Manduca sexta is able to mount a variety of humoral and cellular responses against pathogen attack. Ultimately these prove ineffective against P. luminescens. The pre-treatment of M. sexta with Escherichia coli provides protection against the pathogenesis of P. luminescens. Here, I use RNA interference and Fluorescence-assisted cell sorting techniques to investigate interactions between pathogen and host to further elucidate the roles of various host factors in mounting the immune response. I also investigate the nutrient requirements of the bacteria for pathogenesis. I show data that peptidoglycan recognition protein (PGRP) is essential for the up-regulation of antimicrobial peptides, an important immune defence. I also show that P. luminescens has a requirement for two types of iron during pathogenesis of M. sexta. And lastly I show that P. luminescens is able to avoid phagocytosis, another important immune defence.

Material science is an interdisciplinary area of research, which in part, designs and characterizes new materials. Research is concerned with synthesis, structure, properties, and performance of materials. Discoveries in materials science have significant impact on future technologies, especially in nano-scale applications where the physical properties of nanomaterials are significantly different than their bulk counterparts. The work presented here discusses the use of ferritin, a hollow sphere-like biomolecule, which forms metal oxo-hydride nanoparticles inside its protein shell for uses as a bio-inorganic material.Ferritin is capable of forming and sequestering 8 nm metal-oxide nanoparticles within its 2 nm thick protein shell. A variety of metal-oxide nanoparticles have been synthesized inside ferritin. The work herein focuses on three distinct areas:1) Ferritin's light harvesting properties: namely band gaps. Discrepancies in the band gap energies for ferritin's native ferrihydrite mineral and non-native minerals have been previously reported. Through the use of optical absorption spectroscopy, I resolved the types of band gaps as well as the energy of these band gaps. I show that metal oxides in ferritin are indirect band gap semiconductors which also contain a direct transition. Modifications to the ferrihydrite mineral's band gaps are measured as a result of co-depositing anions into ferritin during iron loading. I demonstrate that these band gaps can be used to photocatalytically reduce gold ions in solution with titanium oxide nanoparticles in ferritin. 2) A new method for manganese mineral synthesis inside ferritin: Comproportionation between permanganate and Mn(II) forms new manganese oxide minerals inside ferritin that are different than traditional manganese oxide mineral synthesis. This reaction creates a MnO2, Mn2O3, or Mn3O4 mineral inside ferritin, depending on the synthesis conditions. 3) Ferritin as an energetic material: Ferritin is capable of sequestering various metals and anions into its interior. Perchlorate, an energetic anion, is sequestered through a co-deposition process during iron loading and is tested with energetic binding materials. Peroxide, which can be used as an oxidant, is also shown to be sequestered within apoferritin and combined with an aluminum based fuel for solid rocket propellants.

L’avènement des nanotechnologies engendre une exposition accrue de l’homme aux nanomatériaux, représentant un risque d’un genre nouveau. A cet égard un grand nombre de recherches porte sur l’étude de leur toxicité. Néanmoins, les questions de dégradation et transformation des nanoparticules dans l’organisme sont encore peu abordées. Des études effectuées au laboratoire ont montré qu’après injection de nanoparticules d’oxyde de fer in vivo, celles-ci sont confinées dans les lysosomes où elles sont dégradées. Une partie de mes travaux de thèse se sont concentrés sur une voie possible de métabolisation des produits de dégradation issus de nanoparticules d’oxydes de fer par l’intermédiaire d’une protéine intervenant dans le métabolisme du fer, la ferritine. Nous avons élaboré plusieurs stratégies afin de détecter et de suivre le transfert de métaux vers la ferritine. Ces travaux ont permis de mettre en évidence un processus de prise en charge des produits de dégradation des nanoparticules d’oxyde de fer à l’échelle moléculaire. Une seconde partie de mes travaux ont été consacré au suivi des produits issus de la dégradation des nanoparticules d’oxyde de fer à l’échelle de l’organisme. La haute concentration endogène en fer rendant impossible ce suivi, une stratégie consistant à marquer les nanoparticules de fer avec un isotope du fer, le 57Fe, a permis de suivre les dynamiques de circulation des produits de dégradation in vivo sur une période de six mois. Nous avons également effectué un double marquage des nanoparticules, du cœur inorganique ainsi que de leur enrobage afin de caractériser leur intégrité in vivo / With the advent of nanotechnology, the exposure of humans to nanomaterials increased, representing a risk of a new kind. Although the potential toxicity of such nanomaterials is extensively studied, their long term fate, biotransformation and degradation in the organism are still poorly understood. It was demonstrated earlier in the laboratory, that after intravenous injection, iron oxide nanoparticles undergo local intracellular degradation within lysosomes. In this context, we are interested in the fate of by products from iron oxide nanoparticles. Part of my thesis has focused on a possible pathway for metabolizing these degradation products through a protein involved in iron metabolism, the ferritin. We first studied, in solution, the degradation processes of iron oxide nanoparticles in the presence of these proteins as well as the iron transfer processes from nanoparticles to ferritin. The difficulty is the high concentration of endogenous iron which makes impossible to demonstrate these in vivo transfers. Thus, we have developed a strategy, using doped iron oxide nanoparticles with a scarce element in the organism, to track these phenomena in vivo. This work highlighted a possible mechanism of biological recycling, remediation and detoxification of nanoparticles mediated by endogenous proteins at the molecular scale. A second part of my work was devoted to develop a multi-scale method to study the life cycle of metal oxide nanoparticles and their by products in organism. The main challenge is to differentiate iron stemming from the nanoparticles from the endogenous iron. This specific tracking problem is routinely encountered in geochemical studies and solved by labelling the target material with minor stable isotopes. Therefore, iron oxide nanoparticles enriched in the minor stable isotope 57Fe were synthetized and injected intravenously in mice to follow dynamic circulations of iron oxide nanoparticles and their byproducts. We have also labelled the coating to track the nanoparticles integrity in mice over a period of six month

Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1 by either over-expression or down-regulation of ALADIN. Our findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore we demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, we show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome.

Diatoms play a fundamental role in marine food webs, and significantly contribute to global primary production and carbon sequestration into the deep ocean. In many offshore areas of the open ocean, iron (Fe) input is low, and its availability often limits phytoplankton biomass. Recently, gene sequences encoding ferritin, a nearly ubiquitous iron storage and detoxifying protein, have been identified in pennate diatoms such as Pseudo-nitzschia, but not in other Stramenopiles (which include centric diatoms, brown algae and some protist plant parasites) or Cryptophyte relatives. Members of this genus readily bloom upon addition of iron to Fe-limited waters, and are known to produce the neurotoxin domoic acid. Until now, the reason for the success of pennate diatoms in the open ocean was uncertain; however, expressing ferritin would allow pennate species to store Fe after a transient input, using it to dominate Fe stimulated algal blooms. Here, the ferritin gene was cloned from the coastal pennate diatom Pseudonitzschia multiseries, overexpressed in Escherichia coli, and purified using liquid chromatography. The ferritin protein sequence appears to encode a non-heme, ferritinlike di-iron carboxylate protein, while gel filtration chromatography and SDS-PAGE indicate that this ferritin is part of the 24 subunit maxi-ferritins. Spectroscopically monitoring the addition of Fe(II) to a buffered ferritin solution shows that the P. multiseries protein demonstrates ferroxidase activity, binding iron and storing it as Fe(III) in excess of 600 equivalents per protein shell. In keeping with the typical stoichiometry of the ferroxidase reaction, oxygen (O₂) is consumed in a 2 Fe:O₂ratio while hydrogen peroxide is produced concurrently. iii Diatoms evolved from secondary endosymbiosis involving eukaryotic red algae; however, a broad phylogenetic comparison suggests that P. multiseries ferritin was likely acquired via lateral gene transfer from cyanobacteria – not from its ancestral endosymbionts. Until recently, no other ferritins have been identified in diatoms, and the protein characterized here is unique in that it seems to be derived from a prokaryotic organism yet it occurs in a marine eukaryote. These findings have direct implications for the success of pennate diatoms in both Fe rich coastal waters and upon Fe addition in the open ocean.

Diatoms play a fundamental role in marine food webs, and significantly contribute to global primary production and carbon sequestration into the deep ocean. In many offshore areas of the open ocean, iron (Fe) input is low, and its availability often limits phytoplankton biomass. Recently, gene sequences encoding ferritin, a nearly ubiquitous iron storage and detoxifying protein, have been identified in pennate diatoms such as Pseudo-nitzschia, but not in other Stramenopiles (which include centric diatoms, brown algae and some protist plant parasites) or Cryptophyte relatives. Members of this genus readily bloom upon addition of iron to Fe-limited waters, and are known to produce the neurotoxin domoic acid. Until now, the reason for the success of pennate diatoms in the open ocean was uncertain; however, expressing ferritin would allow pennate species to store Fe after a transient input, using it to dominate Fe stimulated algal blooms. Here, the ferritin gene was cloned from the coastal pennate diatom Pseudonitzschia multiseries, overexpressed in Escherichia coli, and purified using liquid chromatography. The ferritin protein sequence appears to encode a non-heme, ferritinlike di-iron carboxylate protein, while gel filtration chromatography and SDS-PAGE indicate that this ferritin is part of the 24 subunit maxi-ferritins. Spectroscopically monitoring the addition of Fe(II) to a buffered ferritin solution shows that the P. multiseries protein demonstrates ferroxidase activity, binding iron and storing it as Fe(III) in excess of 600 equivalents per protein shell. In keeping with the typical stoichiometry of the ferroxidase reaction, oxygen (O₂) is consumed in a 2 Fe:O₂ratio while hydrogen peroxide is produced concurrently. iii Diatoms evolved from secondary endosymbiosis involving eukaryotic red algae; however, a broad phylogenetic comparison suggests that P. multiseries ferritin was likely acquired via lateral gene transfer from cyanobacteria – not from its ancestral endosymbionts. Until recently, no other ferritins have been identified in diatoms, and the protein characterized here is unique in that it seems to be derived from a prokaryotic organism yet it occurs in a marine eukaryote. These findings have direct implications for the success of pennate diatoms in both Fe rich coastal waters and upon Fe addition in the open ocean.

Resumo: A beta talassemia heterozigota pode ser decorrente de mutações β 0 ou β + , de acordo com ausência ou redução na produção das cadeias da beta globina, respectivamente. Poucos estudos na literatura correlacionam possíveis efeitos deletérios dessas mutações, quando em heterozigose. A coerança com mutações em genes, não localizados no cluster do gene da β-globina, podem modificar o fenótipo talassêmico. O estresse oxidativo gerado pelo aumento de ERO é um dos mecanismos responsáveis pala aceleração da apoptose celular. Há evidências que o excesso de cadeias alfa, mesmo em pequenas quantidades, seja suficiente para iniciar a geração de ERO e, portanto, estresse oxidativo em beta talassêmicos heterozigotos. Nas formas homozigotas ou com dupla heterozigose os pacientes apresentam anemia grave, transfusão dependente, e a sobrecarga de ferro é uma das mais frequentes e graves complicações nesses indivíduos. Na forma heterozigota a ocorrência de sobrecarga de ferro é rara, porém alterações no perfil do ferro são observadas. O objetivo desse trabalho foi analisar a influência dos níveis de ferritina sérica, das mutações no gene da β-globina, das mutações no gene HFE, da atividade das enzimas de detoxificação GST e CAT e dos polimorfismos das GSTs na expressão fenotípica de indivíduos beta talassêmicos heterozigotos. Foram avaliados 158 portadores de beta talassemia heterozigota diagnosticados previamente por metodologias clássicas. Todos adultos, de origem caucasóide, residentes na região Central do Estado de São Paulo e acompanhados em serviços públicos ou privados da região. O grupo controle foi composto de 24 adultos, caucasóides e residentes na mesma região. A avaliação hematológica foi realizada pelo hemograma, em contadores automatizados de células e quantificação das sub frações de Hb A2 e Hb F por HPLC. O perfil... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Beta thalassemia may occur due to mutations β 0 or β +, according to absence or reduction in the production of beta globin chains, respectively. Few studies have been done correlating possible deleterious effects of these mutations, when in heterozygous. Co-inheritance with mutations in the genes, not located in the cluster of β-globin gene may modify the phenotype of the thalassemic. Stress oxidative generated by the increase of ROS is one of the mechanisms responsible for the acceleration of cell apoptosis. There are evidences that alpha chains in excess, even in small quantities, are sufficient to start ROS generation and thus oxidative stress in heterozygous beta thalassemic. In homozygous form or genetic heterozygous compound present severe anemia, transfusion dependent and iron overload is one of the complications more frequent and severe in these patients. In the heterozygous form the presence of iron overload is rare, but alterations in the profile of iron are observed. The aim of this study was to examine influence of the levels of serum ferritin, the mutations in the β-globin gene, the mutations in the HFE gene, activity of enzymes detoxification, GST and CAT, and polymorphisms of GSTs in the expression phenotypic of individuals heterozygous beta thalassemic. We evaluated 158 patients with beta thalassemia heterozygous previously diagnosed by classic methodologies. They were all adults, Caucasian origin, residents in the Central Region of São Paulo state and accompanied in public or private services of the region. The control group consisted of 24 adults, Caucasians and residents in the same region. Hematologic evaluation was carried out by hemogram, in automated counters of cells and quantification of the subfractions of Hb A2 and Hb F by HPLC; the iron profile was based on the transferrin saturation , calculated on the serum iron and total iron binding capacity... (Complete abstract click electronic access below) / Orientador: Claudia Regina Bonini-Domingos / Coorientador: Eduardo Alves de Almeida / Banca: Elvira Maria Guerra Shinohara / Banca: Ivan Lucena Angulo / Banca: Maria Stella Figueiredo / Banca: Maria Tercília Vilela de Azeredo Oliveira / Doutor

Título: Estresse oxidativo e hormônios esteróides na associação entre Distúrbios Respiratórios do Sono e Doença Aterosclerótica Coronariana Introdução: Estudos epidemiológicos mostram a existência de associação entre a Doença Aterosclerótica Coronariana (DAC) e os Distúrbios Respiratórios do Sono (DRS). Evidencias sugerem que o estresse oxidativo gerado pela hipóxia intermitente sofrida pelos pacientes com DRS pode estar relacionado à progressão da DAC. Os hormônios esteróides testosterona, progesterona e estradiol estão relacionados ao estresse oxidativo, e podem ter papel em ambas as doenças. A enzima glutationa S-tranferase utiliza a molécula antioxidante glutationa na detoxificação de compostos que podem ser formados neste processo. A enzima paraoxonase-1 hidrolisa peróxidos lipídicos, atuando sobre as lipoproteínas de baixa densidade oxidadas (ox-LDL). Ox-LDL são marcadores de peroxidação lipídica, e são importantes na formação da placa aterosclerótica. O vaso dilatador óxido nítrico (NO●) é considerado ateroprotetor e pode estar reduzido, agravando a DAC. Objetivos: Estudar o estresse oxidativo e as alterações fisiopatológicas decorrentes da associação entre DRS e DAC, e avaliar a participação dos hormônios esteroides neste processo. Material e Métodos: 56 pacientes com prévio diagnóstico para Doença Aterosclerótica Coronariana (DAC) e avaliação do Índice de Apneias-hipopneias (IAH) para diagnóstico de Distúrbio Respiratório do sono (DRS) foram divididos em dois grupos, 29 pacientes controles e 27 pacientes com DAC, definidos por apresentarem obstrução coronariana >30%. Foram quantificadas as concentrações séricas dos triglicerídeos, HDL, LDL, ferritina, tranferrina e ferro disponível, assim como dos níveis séricos dos hormônios testosterona, estradiol e progesterona, das enzimas paraoxonase-1 e glutationa S-transferase, e das ox-LDL. Foram quantificadas as concentrações de glutationa total, glutationa reduzida, glutationa oxidada e nitritos e nitratos (medida indireta de NO●) em eritrócitos. A concentração do marcador de dano oxidativo em DNA 8-oxo-7,8-dihidro-2’-desoxiguanosina foi obtida em leucócitos. Resultados: Pacientes com DAC possuem reduzida concentração de nitritos e nitratos. A concentração de 8-OHdG, a atividade da GsT, os níveis de glutationa total, glutationa reduzida e glutationa oxidada, assim com o estradiol e a progesterona, não apresentaram relação com DAC ou DRS. Além do IAH, a redução da testosterona e do ferro disponível estão relacionados a DAC. A redução da atividade da paraoxonase-1 e a maior concentração de ox-LDL são preditores de DAC. A testosterona está relacionada à concentração de ferritina, transferrina e ferro disponível nestes pacientes. A ferritina correlacionou-se positivamente ao dano oxidativo em proteínas e com o IAH, negativamente aos níveis de nitritos e nitratos, e é maior nos pacientes com DAC. Conclusão: Baixos níveis de testosterona e ferro disponível, assim com o aumento da ferritina podem estar relacionados à fisiopatologia da associação entre DRS e DAC. Paraoxonase-1 e ox-LDL são importantes preditores de DAC, mas parecem não estar diretamente relacionados ao IAH nestes pacientes. / Title: Oxidative stress and steroid hormones in the association between Sleep Disordered Breathing and Coronary Artery Disease Introduction: Epidemiological studies have shown a possible association between Coronary Artery Disease (CAD) and Sleep Disordered Breathing (SDB). Evidences suggest that oxidative stress generated by the intermittent hypoxia experienced by patients with sleep disorders may be related to progression of CAD. The steroid hormones testosterone, progesterone and estradiol are related to oxidative stress, and may have a role in both diseases. Glutathione S-transferase uses the antioxidant molecule glutathione in the detoxification of compounds that can be formed in this process. The enzyme paraoxonase-1 hydrolyzes lipid peroxides, acting on oxidized low-density lipoproteins (ox-LDL). Ox-LDL are lipid peroxidation markers, being important for the atherosclerotic plaque formation. The vasodilator nitric oxide (NO●) is considered atheroprotective and can be reduced, aggravating DAC. Objective: Evaluate the oxidative stress and the pathophysiological changes arising from the association between SDB and CAD, and the role of steroid hormones in this process. Material and Methods: 56 patients with prior Coronary Artery Disease (CAD) diagnosis and apnea-hypopnea index (AHI) evaluation for diagnosis of sleep-disordered breathing (SDB) were divided into two groups, 29 control patients and 27 patients with CAD, defined by present a coronary obstruction > 30%. The serum concentration of triglycerides, HDL, LDL, ferritin, transferrin and available iron was obtained, as well as the serum levels of the hormones testosterone, estradiol and progesterone, enzymes paraoxonase-1 and glutathione S-transferase, and ox-LDL. Were measured concentrations of total glutathione, reduced glutathione, glutathione disulfide and nitrites and nitrates (NO● indirect measure) in erythrocytes. The concentration of the 8-oxo-7,8-dihydro-2'-deoxyguanosine, oxidative DNA damage marker, was obtained from leukocytes. Results: CAD patients have reduced concentrations of nitrates and nitrites. The concentration of 8-OHdG, GST activity, levels of total glutathione, reduced glutathione and glutathione disulfide, and estradiol and progesterone, showed no relationship with CAD or SDB. In addition to AHI, the reduction of testosterone and iron available are related to CAD. The reduced activity of paraoxonase-1 and the highest concentration of ox-LDL are CAD predictors. Testosterone is related to the concentration of ferritin, transferrin and iron available in these patients. Ferritin was positively correlated to oxidative damage in protein and with the AHI, and negatively to the levels of nitrites and nitrates, and is higher in CAD patients. Conclusion: Low testosterone levels and iron available, as well as the increase ferritin may be related to the pathophysiology of the association between SDB and CAD. Paraoxonase-1 and ox-LDL are important CAD predictors, but do not seem to be directly related to AHI in these patients.