A obesidade é um importante problema de Saúde Pública e, segundo a Organização Mundial da Saúde (OMS) representa uma epidemia global. Nesse contexto, os adolescentes como foco de mudanças fisiológicas, anatômicas, culturais e sociais representam um grupo com elevado risco de obesidade e suas co-morbidades. O objetivo do presente estudo foi avaliar o possível efeito dos componentes da dieta sobre a atividade antioxidante da proteína paraoxonase (PON1) e o tamanho da HDL em adolescentes. Foram recrutados adolescentes de ambos os sexos, com faixa etária de 10 a 19 anos e de escolas públicas da cidade de São Paulo. Os adolescentes foram distribuídos em três grupos: Eutrófico, Sobrepeso e Obeso, segundo COLE et al. (2000). Após jejum (12-15h) foi coletada uma amostra de sangue e a partir do plasma realizamos as seguintes análises: Perfil lipídico, apo A1, apo B, CETP, Tamanho da HDL (laser- scatering), Atividade da Paraoxonase. Foram coletadas informações antropométricas (peso, altura, circunferência da cintura, porcentagem de gordura corporal). A análise estatística foi realizada com o auxílio do programa SPSS&#174, com valor de significância de p< 0,05. Dos 242 indivíduos elegíveis, 94 (39%) foram meninos e 148 (61%) meninas, com idade média de 13,9 ± 2,3 anos. Baseados no IMC, os adolescentes foram distribuídos em três grupos: Eutrófico: n= 77 adolescentes (32%); Sobrepeso: n= 82 adolescentes (34%) e Obeso: n= 83 adolescentes (34%). Esses grupos não apresentaram diferenças significativas quanto ao sexo, escolaridade da mãe, renda, maturação sexual e história clínica atual. Considerando que os grupos apresentaram diferença significativa entre a idade, as análises estatísticas foram ajustadas por essa variável. As diferenças entre CC e porcentagem de gordura corporal confirmaram os resultados obtidos com o IMC. Verificamos também que os elevados valores de IMC favoreceram a hipertigliceridemia (p= 0,046), e aos baixos valores de HDL-C (p= 0,002). Entretanto, os valores de CETP variaram em função do IMC. Analisando as correlações verificamos que o IMC mostrou correlação positiva com concentração plasmática de colesterol total (r= 0,347 e p= 0,035) e de LDL-C (r= 0,353 e p= 0,032), confirmando o impacto negativo da obesidade sobre os fatores do perfil cardiometabólico. Na análise do TAM HDL não houve diferença significativa entre os 3 grupos. A PON apresentou diferença entre os grupos (p=0,001) o que favorece o seu efeito antioxidante e antiinflamatório. Portanto, os resultados obtidos até a presente data demonstram que adolescentes obesos, mesmo ainda considerados clinicamente saudáveis, apresentam diversos parâmetros antropométricos e bioquímicos alterados, o que indica o elevado risco cardiovascular dessa população. / Obesity is a major public health problem and, according to World Health Organization (WHO) is a global epidemic. In this context, adolescents as the focus of physiological changes, anatomical, cultural and social groups to represent a high risk of obesity and its comorbidities. The aim of this study was to evaluate the possible effect of dietary components on the antioxidant activity of the protein paraoxonase (PON1) and HDL size in adolescents. We recruited adolescents of both sexes, aged from 10 to 19 years and public schools in São Paulo. The adolescents were divided into three groups: Well-nourished, overweight and obesity, according to Cole et al. (2000). After fasting (12-15h) was collected and a blood sample from the plasma to the following analysis: lipid profile, apo A1, apo B, CETP, HDL size (laser-scatering), of paraoxonase activity. Data were collected anthropometric (weight, height, waist circumference, percentage body fat). Statistical analysis was performed with the SPSS software programSPSS&#174, with significance level of p <0.05. Of the 242 eligible individuals, 94 (39%) were boys and 148 (61%) girls, mean age 13.9 ± 2.3 years. Based on BMI, adolescents were divided into three groups: Eutrophic: n = 77 adolescents (32%) Overweight: n = 82 adolescents (34%) and obese: n = 83 adolescents (34%). These groups showed no significant differences regarding sex, maternal education, income, sexual maturation, and current medical history. Whereas the groups showed significant difference between age, statistical analysis was adjusted for this variable. The differences between CC and percentage of body fat confirmed the results obtained with BMI. We also found that high BMI values favored hipertigliceridemia (p = 0.046), and low HDL-C (p = 0.002). However, the values of CETP varied according to BMI. Analyzing the correlations we found that BMI was correlated positively with plasma total cholesterol (r = 0.347 and p = 0.035) and LDL-C (r = 0.353 and p = 0.032), confirming the negative impact of obesity on cardiovascular risk factors . In the analysis of TAM HDL no significant difference among the three groups. The PON was different between groups (p = 0.001) which favors the antioxidant and anti-inflammatory effect. Therefore, the results obtained to date show that obese adolescents, even those deemed clinically healthy, have several anthropometric and biochemical changes, which indicates that the high cardiovascular risk population.

A obesidade é um importante problema de Saúde Pública e, segundo a Organização Mundial da Saúde (OMS) representa uma epidemia global. Nesse contexto, os adolescentes como foco de mudanças fisiológicas, anatômicas, culturais e sociais representam um grupo com elevado risco de obesidade e suas co-morbidades. O objetivo do presente estudo foi avaliar o possível efeito dos componentes da dieta sobre a atividade antioxidante da proteína paraoxonase (PON1) e o tamanho da HDL em adolescentes. Foram recrutados adolescentes de ambos os sexos, com faixa etária de 10 a 19 anos e de escolas públicas da cidade de São Paulo. Os adolescentes foram distribuídos em três grupos: Eutrófico, Sobrepeso e Obeso, segundo COLE et al. (2000). Após jejum (12-15h) foi coletada uma amostra de sangue e a partir do plasma realizamos as seguintes análises: Perfil lipídico, apo A1, apo B, CETP, Tamanho da HDL (laser- scatering), Atividade da Paraoxonase. Foram coletadas informações antropométricas (peso, altura, circunferência da cintura, porcentagem de gordura corporal). A análise estatística foi realizada com o auxílio do programa SPSS&#174, com valor de significância de p< 0,05. Dos 242 indivíduos elegíveis, 94 (39%) foram meninos e 148 (61%) meninas, com idade média de 13,9 ± 2,3 anos. Baseados no IMC, os adolescentes foram distribuídos em três grupos: Eutrófico: n= 77 adolescentes (32%); Sobrepeso: n= 82 adolescentes (34%) e Obeso: n= 83 adolescentes (34%). Esses grupos não apresentaram diferenças significativas quanto ao sexo, escolaridade da mãe, renda, maturação sexual e história clínica atual. Considerando que os grupos apresentaram diferença significativa entre a idade, as análises estatísticas foram ajustadas por essa variável. As diferenças entre CC e porcentagem de gordura corporal confirmaram os resultados obtidos com o IMC. Verificamos também que os elevados valores de IMC favoreceram a hipertigliceridemia (p= 0,046), e aos baixos valores de HDL-C (p= 0,002). Entretanto, os valores de CETP variaram em função do IMC. Analisando as correlações verificamos que o IMC mostrou correlação positiva com concentração plasmática de colesterol total (r= 0,347 e p= 0,035) e de LDL-C (r= 0,353 e p= 0,032), confirmando o impacto negativo da obesidade sobre os fatores do perfil cardiometabólico. Na análise do TAM HDL não houve diferença significativa entre os 3 grupos. A PON apresentou diferença entre os grupos (p=0,001) o que favorece o seu efeito antioxidante e antiinflamatório. Portanto, os resultados obtidos até a presente data demonstram que adolescentes obesos, mesmo ainda considerados clinicamente saudáveis, apresentam diversos parâmetros antropométricos e bioquímicos alterados, o que indica o elevado risco cardiovascular dessa população. / Obesity is a major public health problem and, according to World Health Organization (WHO) is a global epidemic. In this context, adolescents as the focus of physiological changes, anatomical, cultural and social groups to represent a high risk of obesity and its comorbidities. The aim of this study was to evaluate the possible effect of dietary components on the antioxidant activity of the protein paraoxonase (PON1) and HDL size in adolescents. We recruited adolescents of both sexes, aged from 10 to 19 years and public schools in São Paulo. The adolescents were divided into three groups: Well-nourished, overweight and obesity, according to Cole et al. (2000). After fasting (12-15h) was collected and a blood sample from the plasma to the following analysis: lipid profile, apo A1, apo B, CETP, HDL size (laser-scatering), of paraoxonase activity. Data were collected anthropometric (weight, height, waist circumference, percentage body fat). Statistical analysis was performed with the SPSS software programSPSS&#174, with significance level of p <0.05. Of the 242 eligible individuals, 94 (39%) were boys and 148 (61%) girls, mean age 13.9 ± 2.3 years. Based on BMI, adolescents were divided into three groups: Eutrophic: n = 77 adolescents (32%) Overweight: n = 82 adolescents (34%) and obese: n = 83 adolescents (34%). These groups showed no significant differences regarding sex, maternal education, income, sexual maturation, and current medical history. Whereas the groups showed significant difference between age, statistical analysis was adjusted for this variable. The differences between CC and percentage of body fat confirmed the results obtained with BMI. We also found that high BMI values favored hipertigliceridemia (p = 0.046), and low HDL-C (p = 0.002). However, the values of CETP varied according to BMI. Analyzing the correlations we found that BMI was correlated positively with plasma total cholesterol (r = 0.347 and p = 0.035) and LDL-C (r = 0.353 and p = 0.032), confirming the negative impact of obesity on cardiovascular risk factors . In the analysis of TAM HDL no significant difference among the three groups. The PON was different between groups (p = 0.001) which favors the antioxidant and anti-inflammatory effect. Therefore, the results obtained to date show that obese adolescents, even those deemed clinically healthy, have several anthropometric and biochemical changes, which indicates that the high cardiovascular risk population.

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Paraoxonase (PON) 1 is a high density lipoprotein (HDL) - bound antioxidant enzyme that was originally discovered and better known for its role in protecting against organophosphate (OP) - induced neurotoxicity. In the past two decades, the enzyme has gained prominence as a protective agent against atherosclerosis on account of increasing evidence that it accounts for many of the anti-atherogenic roles attributed to HDL. PON1 is a polymorphic enzyme displaying a high variability in human populations which is associated with a considerable degree of inter-individual differences in enzyme phenotype that translates to differential risk for OP toxicity and cardiovascular disease (CVD). In a series of studies and analyses, this thesis describes investigations regarding the possible involvement of PON 1 in the risk for CVD in a mixed ancestry population from Bellville, Western Cape, South Africa. This was done by evaluating the distribution of PON1 coding region polymorphisms (Q192R and L55M) and their influence on PON1 phenotype as well as the latter‟s relation to CVD risk factors (oxidative stress, inflammation and atherogenic dyslipidemia) and possible involvement in early CVD assessed by measuring intima media thickness of the carotid artery (CIMT). Since PON1 is increasingly measured in samples that have been stored for varied periods of time, the main study was preceded by a pilot study evaluating the influence of baseline conditions on the stability of PON 1 activity and antioxidant status in human sera stored for up to 12 months. It was shown that baseline glycemic status enhances the degradation of antioxidants in stored samples with indications of also accelerating the decline of PON1 levels and activity. Thus baseline glycemic status should be a factor to be considered in analyses involving stored samples. The Q192R polymorphism was found to be the functional variant influencing both concentration and activity of plasma PON1. Contrary to expectation, the L55M was nonfunctional, possibly due to its unusual distribution in this population where the 55M (83%) allele overwhelmingly predominated over the L55 allele. The R allele was the more frequent (60.4%) of the 192 polymorphism. The R allele has previously been associated with less efficient breakdown of lipid peroxides and a subsequent higher risk for atherosclerotic heart disease while the 55M is recognized as a “low concentration/activity” variant. Thus the predominant PON1 genotype distribution in this population constitutes a risk profile that may relate to increased risk for CVD. The risk for CVD was confirmed to be very high in this population indicated by high prevalence of the metabolic syndrome (48%) and its key components (and CVD risk factors) diabetes (28%), obesity (53%) and high blood pressure (57%). Paraoxonase activity associated inversely with indices of inflammation (high sensitive C- reactive protein [hs-CRP] and leptin) and oxidative stress (oxidized low density lipoprotein [LDL]) and directly with adiponectin and markers of systemic antioxidant status. These findings suggest that low paraoxonase-I activity contributes to increased cardiovascular risk possibly via involvement in early atherogenesis. However, only a modest inverse relation was observed between PON1 phenotype and CIMT thus suggesting that PON1 may not play a major role in early atherosclerosis. Taken together, the findings presented in this thesis demonstrate the presence of a risk PON1 genotypic profile and indication that the enzyme may play a role in the enhanced CVD risk in this population possibly via interactions with inflammation and oxidative stress. However, conclusive evidence for the involvement of PON1 in early CVD was not demonstrated indicating a need to explore the participation of PON1 in later stages of CVD. / AFRIKAANSE OPSOMMING: Paraoksonase (PON) 1 is 'n antioksidant ensiem wat aan HDL gebind is. Oorspronklik is dit ontdek en het bekend geword as 'n beskermer teen organofosfaat (OF)-gedrewe neurotoksisiteit. In die afgelope twee dekades het die ensiem belangrik geraak as 'n beskermer teen arterosklerose as gevolg van toenemende bewyse dat dit 'n belangrike rol speel in die beskermende effekte van HDL teen arterosklerose. PON1 is 'n polimorfiese ensiem wat groot variasie toon in verskillende populasies. Daar is ook inter-individuele verskille in ensiem fenotipe wat uitloop op 'n differensiele risiko vir OF toksisiteit en kardiovaskulêre hartsiekte (KVH). Hierdie tesis beskryf 'n reeks analises en ondersoeke betreffende die moontlike betrokkenheid van PON1 in die risiko vir KVH in 'n gemengdeafkoms populasie van Bellville, Wes-Kaap, Suid Afrika. Dit was gedoen deur die evaluering van die verspreiding van die PON-1 koderende omgewing polimorfismes (Q192R en L55M), hulle invloed op PON1 fenotipe en laasgenoemde se verhouding tot KVH risikofaktore (oksidatiewe stress, inflammasie en arterogeniese dislipedimie) en moontlike voorkoms in vroeë kardiovaskulêre siekte bepaal deur die meting van die intima media dikte van die karotied slagaar. Aangesien PON1 al hoe meer gemeet word in monsters wat vir verskeie tydperke gestoor word, was die hoofstudie voorafgegaan deur 'n loodsstudie wat die invloed van basislyn kondisies op die stabiliteit van PON1 aktiwiteit en antioksidant status in menslike sera wat vir tot 12 maande gestoor was, bepaal het. Dis is duidelik aangetoon dat basislyn glisemiese status die afbraak van antioksidante in gestoorde monsters verhoog het, asook aanduidings van die afname van PON1 vlakke en aktiwitetit. Basislyn glisemiese status behoort dus ook as 'n faktor ingereken te word in analises van gestoorde monsters. Die Q192R polimorfisme is aangetoon om 'n funksionele variant te wees wat beide die konsentrasie asook die aktiwiteit van PON1 beïnvloed het. Anders as wat verwag is, was die L55M polimorfisme nie-funksioneel, moontlik as gevolg van sy ongewone distribusie in hiedie populasie waar die voorkoms van die 55M (83%) alleel die L55 alleel oorheers het. Die R alleel was die mees algemene (60.4%) van die 192 polimorfisme. Die R alleel is voorheen reeds geassosieer met minder effektiewe afbraak van lipied peroksides en gevolglike hoër voorkoms van arteriosklerotiese hartsiekte, terwyl die 55M erken word as 'n “lae konsentrasie/aktiwiteit” variant. Die oorheersende PON1 genotipe distribusie in hierdie populasie behels dus 'n risikoprofiel wat betrekkking mag hê op verhoogde KVH. Die risiko vir KVH was bevestig om baie hoog te wees in hierdie populasie, soos aangedui deur 'n hoë voorkoms van die metaboliese sindroom (48%) en die sleutelkomponente daarvan (insluitend KVH risikofaktore), diabetes (28%), obesiteit (53%) en hipertensie (57%). Paraoksinase aktiwiteit was omgekeerd geassosieer met indekse van inflammasie (hoë C-reaktiewe proteïen [hs-CRP] en leptien) en oksidatiewe stres (geoksideerde lae digtheid lipoproteïen [LDL], en direk geassosieer met adiponektien en merkers van sistemiese antioksidantstatus. Hierdie bevindings mag aandui dat lae paraoksonase-1 aktiwiteit bydra tot verhoogde kardiovaskulêre risiko, moontlik via betrokkenheid in vroeë arterogenese. Slegs 'n klein omgekeerde verhouding is egter waargeneem tussen die PON1 fenotipe en karotied intima media dikte, wat mag aandui dat PON1 nie 'n beduidende rol speel in vroeë arterosklerose nie. In geheel, die bevindinge voorgedra in hierdie tesis demonstreer die voorkoms van 'n risiko PON1 genotipiese profiel wat 'n aanduiding mag wees dat die ensiem 'n rol mag speel in die verhoogde KVH risiko in hierdie populasie, moontlik deur interaksies met inflammasie en oksidatiewe stress. Afdoende bewys van die betrokkenheid van PON1 in vroeë KVH was egter nie gedemonstreer nie, wat die nodigheid aandui om die deelname van PON1 in latere stadiums van KVH te ondersoek.

Oral and oropharyngeal squamous cell carcinoma (OOSCC) is a malignant neoplasm of epithelial origin that accounts for 90 to 95% of tumors in oral cavity. Alcohol and tobacco consumption are main risk factors, but the formation of reactive oxygen species (ROS) and presence of chronic inflammatory processes have been shown to favor the carcinogenesis process. Human serum paraoxonase 1 (PON1) is a protein with an important antioxidant action and prevents oxidative stress induced by ROS, in turn, high levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) are commonly found in inflammatory processes, and changes in these proteins have been related to development of different neoplasms. Present study aims to investigate the prognostic value of functional polymorphisms in PON1, TNF-α and TGF-β genes in OOSCC. This is a prospective cohort study with patients attended at the Advanced Oncology Center of the North-Riograndense League against Cancer. Data collection of clinical variables was done through the form: gender, age, tumor site, TNM (primary tumor, regional nodule and distant metastasis) classification, clinical stage; and through interview: smoking habits and alcohol intake by the patient. A total of 163 samples from patients with OOSCC and 146 control samples were genotyped by real-time PCR. It was observed that 76.1% of the population was males, 84% older than 52 years, with a more frequent intra-oral clinical presentation (53.4%), in the tongue region (21.5%), tumors greater than 4cm (56.45%), presence of nodal involvement (58.9%) and stages III and IV (79.15%). There was a positive association between drinking and smoking habits in patients with OOSCC and between clinical stage and tumor site (p <0.05). The polymorphisms were in Hardy-Weinberg equilibrium, with exception of rs662 of PON1. TNF-α wild-type GG homozygous genotype (rs1800629) was associated with intra-oral lesions, clinical stage of the most advanced disease (III and IV), and decreased overall disease survival, whereas the polymorphic AA genotype was associated with lip lesion, clinical stage I and II and a longer overall disease survival (p <0.05). It was observed association of TGF-β polymorphic AG and AA genotypes (rs1800469) with larger diameter tumors (T3 and T4) (p <0.05). Finally, the polymorphic TT genotype of PON1 (rs662) in recessive model was associated with a shorter disease survival time within threshold of significance (p = 0.05). In view of the findings, it is suggested that wild-type GG homozygous genotype of TNF-α rs1800629 and TGF-β rs1800469 polymorphic AG and AA genotypes may exert an influence on more aggressive biological behavior of OOSCC and that AG genotype of TNF-α rs1800629 and TT genotype of PON1 rs662 could be prognostic markers in OOSCC. In the clinical practice of oncology, these genotypes can be used to perform early diagnosis, knowledge of the biological behavior of the tumor and choice of appropriate individualized therapy / O carcinoma de células escamosas oral e orofaríngeo (CCEO) é uma neoplasia maligna de origem epitelial que representa 90 a 95% dos tumores da cavidade oral. O consumo de álcool e de tabaco são os principais fatores de risco, mas a formação de espécies reativas de oxigênio (EROs) e a presença de processos inflamatórios crônicos têm-se mostrado favorável ao processo de carcinogênese. A paraoxonase de soro humano 1 (PON1) é uma proteína com importante ação antioxidante e previne o estresse oxidativo induzido pelas EROs, por sua vez, elevados níveis do fator de necrose tumoral-alfa (TNF-α) e do fator de crescimento transformante-beta (TGF-β) são comumente encontrados em processos inflamatórios, e alterações nessas proteínas têm sido relacionadas com o desenvolvimento de diferentes neoplasias. O presente estudo tem por objetivo investigar o valor prognóstico dos polimorfismos funcionais nos genes da PON1, TNF-α e TGF-β no CCEO. Trata-se de um estudo coorte prospectivo com pacientes atendidos no Centro Avançado de Oncologia da Liga Norte-Riograndense contra o Câncer. Realizou-se a coleta de dados das variáveis clínicas por meio de formulário: gênero, idade, localização do tumor, classificação TNM (Tumor primário, nódulo regional e metástase à distância), estadiamento clínico (EC); e por meio de entrevista: hábitos de fumo e ingestão alcoólica pelo paciente. Foram genotipadas 163 amostras de pacientes com CCEO e 146 amostras controle por meio de PCR em tempo real. Observou-se que 76,1% da população era do gênero masculino, sendo 84% com mais de 52 anos, com apresentação clínica mais frequente intra-oral (53,4%), na região da língua (21,5%), tumores maiores que 4cm (56,45%), presença de envolvimento nodal (58,9%) e em estágios III e IV (79,15%). Evidenciou-se associação positiva entre os hábitos de beber e fumar com pacientes portadores de CCEO e entre o EC e a localização do tumor (p<0,05). Os polimorfismos encontravam-se em equilíbrio de Hardy-Weinberg, com exceção do rs662 da PON1. O genótipo homozigoto selvagem GG do TNF-α (rs1800629) associou-se com lesões intra-orais, EC da doença mais avançado (III e IV) e menor sobrevida global da doença, enquanto o genótipo AA polimórfico associou-se a lesão de lábio, EC I e II e maior sobrevida global da doença (p<0,05). Observou-se associação dos genótipos AG e AA polimórfico do TGF-β (rs1800469) com tumores de maior diâmetro (T3 e T4) (p < 0,05). Por fim, o genótipo TT polimórfico da PON1 (rs662) no modelo recessivo apresentou associação com menor tempo de sobrevida da doença dentro do limiar de significância (p=0,05). Diante dos achados, sugere-se que o genótipo GG selvagem do rs1800629 do TNF-α e os genótipos AG e AA polimórfico do rs1800469 do TGF-β podem exercer influência no comportamento biológico mais agressivo do CCEO e que o genótipo AG do rs1800629 do TNF-α e o genótipo TT polimórfico do rs662 da PON1 poderiam ser marcadores com valor prognóstico no CCEO. Na prática clínica da oncologia, esses genótipos podem ser utilizados para realização de diagnóstico precoce, conhecimento do comportamento biológico do tumor e escolha da terapêutica individualizada adequada. / Lagarto, SE

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2016-09-13T14:06:33Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_anelize_felix.pdf: 680064 bytes, checksum: ce7bdb70069b351d37170f2fbe481b60 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2016-09-13T14:14:27Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_anelize_felix.pdf: 680064 bytes, checksum: ce7bdb70069b351d37170f2fbe481b60 (MD5) / Made available in DSpace on 2016-09-13T14:14:27Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tese_anelize_felix.pdf: 680064 bytes, checksum: ce7bdb70069b351d37170f2fbe481b60 (MD5) Previous issue date: 2014-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / O surgimento dos neoplasmas mamários bem como o estabelecimento das metástases está relacionado com uma série de fatores, dentre eles destaca-se a liberação de radicais livres. A paraoxanase é uma enzima produzida pelo fígado que é capaz de de remover os produtos da peroxidação lipídica. O uso de substâncias consideradas antioxidantes vem sendo uma alternativa para o combate ao estresse oxidativo. A copaíba é uma planta usada com várias finalidades e atualmente autores atribuem a ela potencial antioxidante. O objetivo deste trabalho foi estabelecer o perfil oxidativo de cães portadores de tumor de mama e avaliar o uso do óleo resina de copaíba como terapia adjuvante no tratamento de modelos biológicos portadores de tumores mamários induzidos quimicamente. Foram coletadas amostras sanguíneas de 50 cães com tumores mamários, onde foi verificado a atividade da enzima PON1 e a capacidade antioxidante total (CAT). O uso do óleo resina de copaíba foi estudado em ratos Wistar com e sem tumores induzidos, nos quais foi avaliado os níveis de enzimas hepáticas e também a atividade da PON1. Foram também realizados testes de citotoxicidade in vitro com diferentes concentrações do óleo resina de copaíba. Foi possível observar que cães com tumor de mama apresentam redução na atividade da enzima PON1 e também na CAT. O óleo resina de copaíba apresentou capacidade de inibir o crescimento de linhagens celulares de tumor de mama, entretanto, este estudo não pode definir sua atividade no controle destes tumores in vivo. / The occurrence of mammary tumors, as well as metastatic establishment, is associated with a series of factors, foremost among which are free radicals. Paraoxanase is an enzyme produced by the liver, capable of removing by products of lipid peroxidation. The use of antioxidant substances is becoming an alternative measure in combating oxidative stress. Copaiba oil is used for various medical reasons, and it is believed to have antioxidant potential. In this light, this study assesses the oxidative profile of dogs suffering from mammary tumors, and evaluates the viability of using copaiba oil as an adjuvant in treating this disease. Blood samples from 50 dogs with mammary tumors were obtained and PON1 activity and total antioxidant capacity (TAC) assessed. The use of copaiba oil was also assessed regarding its safety and action in a rat model for mammary tumors. PON1 activity and hepatic function was also assessed. Furthermore, copaiba oil was assessed in vitro regarding its toxicity in normal or cancerous cell lines. Dogs with mammary tumors had lower levels of PON1 activity than healthy peers, and the TAC was directly correlated. Copaiba oil did inhibit cancerous cell growth in vitro, but this study could not determine its effects in tumors in vivo.

No description available.

Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes the oxons of several organophosphorous insecticides (e.g. paraoxon, diazoxon and chlorpyrifos-oxon) and metabolizes lipid peroxides of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility of organophosphate toxicity and cardiovascular disease. The objective of this study was to determine associations of PON1 status (i.e. genotype and activity levels) with atherosclerosis (ATH) in individuals from the Southeastern United States. An additional objective was to determine whether PON1 genotype and/or PON1 activity levels influence the capacity of PON1 to metabolize chlorpyrifos-oxon (CPO) at a relatively low concentration. Data indicated increasing PON1 activity assessed by hydrolysis of phenyl acetate is associated with decreased odds of ATH. Furthermore, neither PON1 genotype nor PON1 activity levels influence capacity of PON1 to metabolize CPO at a relatively low concentration.

No description available.

No description available.

A enzima Paraoxonase-1 (PON1) possui atividades paraoxonase, arilestearase e lactonase, entre outras. É a mais estuda da família das PONs que é composta pela PON1, PON2 e PON3. Sugere-se, que todas atuam inibindo o processo de peroxidação lipídica de moléculas como a lipoproteína de baixa densidade (LDL) e alta densidade (HDL), caracterizando assim um possível papel anti-aterogênico. O gene da PON1 apresenta dois sítios polimórficos, com a troca de uma Gln192Arg (Q/R) e Met55Leu, que estão associados com diferenças na atividade e concentrações séricas da enzima. Por sua vez, indivíduos soropositivos para o HIV-1 apresentam alterações do metabolismo lipídico, que poderiam estar associados a alterações na atividade da PON1 e a terapia antirretroviral (TARV) com inibidores de protease (IP). O objetivo do estudo foi determinar as atividades séricas da PON1 e da arilestearase (ARE), e as freqüências alélicas dos polimorfismos genéticos da PON1 192QR e 55LM, e ainda, avaliar a correlação destes parâmetros com as alterações lipídicas em indivíduos soropositivos para o HIV-1 tratados com IP. No período de Setembro de 2009 até Junho de 2012, 174 indivíduos soropositivos e 46 soronegativos para o HIV-1 foram estudados. Foi realizada a genotipagem dos polimorfismos da PON1 192QR e 55LM através de PCR-RFLP. A atividade sérica da PON1/ARE foi avaliada por espectrofotometria empregando-se como substratos o paraoxon e o fenilacetato, respectivamente. O RNA-HIV-1 foi quantificado pelo método NASBA, e os linfócitos T-CD4+ e T-CD8+ por citometria de fluxo. Os níveis séricos de colesterol total, HDL, LDL, triglicérides (TG), ApoA1 e ApoB100 foram determinados e os anticorpos IgG anti-oxLDL por ELISA. A atividade sérica da PON1 foi inferior nos grupos de soropositivos, p<0,05, porém, a atividade ARE não apresentou diferenças entre os grupos estudados, p>0,05. Ambas as atividades não apresentaram relação com os genótipos PON1 192QR e 55LM, e estes genótipos apresentaram uma freqüência alélica semelhante ao grupo de soronegativos. Os níveis séricos de TG foram superiores nos grupos de soropositivos com TARV, p<0,05, enquanto o grupo tratado com IP apresentou níveis séricos de HDL e Apo-A1 inferiores aos demais grupos, p<0,05. Níveis séricos de Apo-B100, IgG anti-oxLDL, e o índice de risco aterogênico foram superiores no grupo tratado com IP, p<0,05. Concluí-se, que indivíduos soropositivos para o HIV-1 apresentaram alterações no metabolismo lipídico, principalmente nos tratados com IP, que adicionalmente apresentaram um maior índice de risco aterogênico e maiores níveis de anticorpos IgG anti-oxLDL. Estas alterações não apresentaram relação com os polimorfismos PON1 192QR e 55LM da PON1, e demonstraram que a atividade da enzima PON-1 esta diminuída em indivíduos soropositivos para o HIV-1 / The enzyme Paraoxonase-1 (PON1) has paraoxonase (PON), arylesterase (ARE) and lactonase activities, among others. It is the most studied member of PON family which is composed of PON1, PON2 and PON3. It is suggested that all members acts by inhibiting the peroxidation of lipid molecules as the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), characterizing a potential anti-atherogenic effect. The PON1 gene has two mainly polymorphic sites, with an exchange of Gln192Arg (Q/R) and Met55Leu (L/M), which are associated with differences in activity and serum concentrations of the enzyme. In turn, seropositive individuals for HIV-1 show changes in lipid metabolism, which could be associated with changes in the activity of PON1 and highly active antiretroviral therapy (HAART) with protease inhibitors (PI). The aim of this study was to determinate the serum PON and ARE activities of PON1, the allele frequencies of PON1 192QR and PON1 55LM genetic polymorphisms and evaluate the correlation between these parameters and lipid abnormalities in seropositive patients for HIV-1 treated with IP. In the period from September 2009 until June 2012, 174 seropositive individuals and 46 soronegative individuals for HIV-1 were studied. We performed PON1 192QR and 55LM genotyping by PCR-RFLP. Serum activities PON and ARE of PON1 were evaluated by spectrophotometry using paraoxon and phenylacetate, respectively, as substrates. The HIV-1-RNA was quantified by the NASBA method, and lymphocytes T-CD4+ and T-CD8+, by flow cytometry. Serum levels of total cholesterol, HDL, LDL, triglycerides (TG), apoA1 and ApoB100 were determined. IgG anti-oxLDL antibodies were quantified by ELISA. The serum PON1 activity was lower in the seropositive group, p<0.05, however, ARE activity did not differ between groups, p>0.05. Both activities had no relation with the PON1 192QR and PON1 55LM genotype, and these individuals showed an allele frequency similar to the seronegative group. Serum levels of TG were higher in groups of HIV-positive with HAART, p<0.05, while the IP-treated group showed serum levels of HDL and ApoA1 lower than other groups, p <0.05. Serum levels of ApoB100, IgG anti-oxLDL antibodies, and atherogenic risk indices were higher in the group treated with PI, p<0.05. It was concluded that individuals HIV-1-infected showed changes in lipid metabolism, especially in those treated with IP, which additionally showed a higher rate of atherogenic risk and higher levels of IgG anti-oxLDL antibodies. These changes did not correlated with PON1 192QR and 55LM polymorphisms and demonstrated that the activity of PON1enzyme is decreased in individuals seropositive for HIV-1