Influência do ácido α-lipóico na adaptação antioxidante ao exercício físico em ratas wistar hígidas e ovariectomizadas

Introdução: Os hormônios estrogênicos possuem importante papel na defesa contra as espécies reativas do oxigênio, fato que se evidencia na maior incidência de doenças cardiovasculares e neurodegenerativas após a menopausa. O exercício físico melhora as defesas antioxidantes, contudo em altas cargas e em baixas concentrações de estrógeno possui efeito aditivo ao dano oxidativo. O ácido α-lipóico possui uma ampla gama de ação antioxidante e poderia contribuir para diminuição do dano nestas condições. Objetivo: O objetivo deste estudo é caracterizar a ação do ácido α-lipóico sobre a adaptação antioxidante e funções reprodutivas de ratas submetidas a natação moderada. Material e métodos: Os animais foram submetidos a natação diária (1 hora) e sacrificados após 30, 60 e 90 dias. Os animais foram divididos em controles sedentários e exercitados; suplementados (ácido α-lipóico 100mg/Kg/dia) sedentários e exercitados e animais ovariectomizados e suplementados com ácido lipóico. Avaliou-se diariamente o ciclo estral e os seguintes marcadores de estresse oxidativos foram mensurados em fígado e sangue: atividade enzimática da SOD, GPx e CAT, além do SRAT e GSH. Resultados: O protocolo de exercício aumentou a duração do ciclo estral no grupo controle exercitado, sobretudo na fase diestral. Neste mesmo grupo, houve diminuição da lipoperoxidação com melhora da atividade antioxidante da SOD e GPx. O grupo exercitado e suplementado não apresentou alteração na duração do ciclo estral e manteve os benefícios sobre o sistema antioxidante antes observado nos animais exercitados. A suplementação antioxidante juntamente com a natação em períodos superiores a 30 dias, diminuiu o processo de adaptação antioxidante quando comparado aos animais somente exercitados. Nos animais ovariectomizados, o exercício e a suplementação com ácido lipóico não promoveu adaptação antioxidante ao contrário dos demais grupos. Conclusão: O aumento na duração do ciclo estral e a melhora nos marcadores de estresse oxidativo seriam uma resposta adaptativa frente ao exercício moderado. O ácido lipóico impediu a alteração no ciclo induzida pelo exercício, mas preservou a melhoria no sistema antioxidante. A depleção estrogênica provocada pela ovariectomia eleva o potencial de dano oxidativo gerado pelo exercício. A ação antioxidante do LA na presença de estrógeno diminuiu excessivamente o dano oxidativo, comprometendo a adaptação antioxidante a natação. Nos animais ovariectomizados, contudo, o AL promoveu adaptação antioxidante ao exercício

Estudo do efeito dos metabólitos do benzeno e tolueno sobre as mitocôndris cerebrais e hepáticas de ratos

Aim: The aim of this work was to investigate the hypothesis that catechol and 3MC inhibit FADH2-linked basal respiration in mitochondria isolated from rat liver and brain homogenates. Moreover, catechol ability to induce DNA damage in rat brain cells through the comet assay (alkaline single-cell gel electrophoresis assay) was also observed. Methods: Two different catechols were evaluated: pirocatechol (derived from benzene) and 3-methylcatechol (derived from toluene); rat liver and brain homogenates were incubated with 1mM catechol at pH 7.4 for up to 30 minutes. After that, mitochondrial fractions were isolated by differential centrifugation. Basal oxygen uptake was measured using a Clark-type electrode after the addition of 10 mM sodium succinate for a period of 12 minutes. In additional experiments, rat brain cells were treated with 1, 5 and 10mM pirocatechol for up to 20 minutes at 37º C, and submitted to electrophoresis. Results: Catechols (pirocatechol and 3methylcatechol) induced a time-dependent partial inhibition of FADH2-linked basal mitochondrial respiration. Indeed, pirocatechol was able to produce a dosedependent DNA oxidative damage in rat brain cells by 2 and 4 injury levels. These results suggest that reactive oxygen species generated by the oxidation of catechols, induced an impairment on mitochondrial respiration and a DNA damage, which might be related to their citotoxicity. Conclusion: Catechols produced an inhibition of basal respiration associated to FADH2 in isolated liver and brain mitochondria; 3-methylcatechol, at the same concentration, produced similar toxicity in the mitochondrial model. Indeed, pirocatechol induced a DNA damage in rat brain cells, mainly observed in comets formation and consequent DNA degradation

Avaliação dos parâmetros de estresse oxidativo no lúpus eritematoso

OBJECTIVE: The aim of this work was to analyse some oxidative stress parameters in patients of Systemic Lúpus Erythematosus. PATIENTS AND METHODS: Determinations of reduced glutathione content in whole blood were carried out. The activity of superoxide dismutase, gluthatione peroxidase and catalase in erythrocytes and the concentration of reactive substances of acid thiobarbituric in plasma of patients female (n =19) with SLE no activity of disease (Mex-SLEDAI < 2), with average ages of 32 ± 11 years, through the spectrophotometrical methods and from healthy individuals (n =30). Statistical data were analyzed by student t-test, p<0,05. RESULTS: Our data indicated a significant decrease on the activity of catalase and significant increase on the concentration of reactive substances of acid thiobarbituric in patients with SLE comparing with healthy individuals. There was no significant difference in other parameters. CONCLUSION: The results showed that oxidative stress has a role in the pathogenesis of the disease in SLE, even in patients without active disease.

Avaliação in vitro e in vivo da Atividade Antioxidante do Extrato Hidroetanólico de Folhas de Turnera ulmifolia Linn. var. elegans (Turneraceae)

Recently, it has been a increasing interest in the antioxidative role of natural products to aid the endogenous protective biological systems against the deleterious effects of oxygen (ROS) and nitrogen (RNS) reactive species. Many antioxidant compounds, naturally occurring from plant sources. Natural antioxidants can protect and prevent the human body from oxidative stress and retard the progress of many diseases in which free radical are involved. Several plants used in the folk medicine to treat certain disorders that are accompanied by inflammation and other pharmacological properties have been proved their attributed properties, such antioxidant activity. Turnera ulmifolia Linn. var. elegans (Turneraceae), frequently employed by population as a medicinal plant, demonstrated antioxidant activity by in vitro and in vivo assays, using its leaf hydroethanolic extract (10%) he in vitro DPPH radical-scanvenging activity showed a strong antioxidant activity (86.57% ± 0.14), similar to Carduus marianus and catequine effects. For the in vivo assays, adult female Wistar rats (n=48) with carbon tetrachloride hepatic injury induced (2,5mL/kg i.p.) were used, Six groups or rats were uses (n=8) [G1 = control (1,25 mL/kg i.p. vehicle); G2 = CCl4 (2,5 mL/kg i.p.); G3 = CCl4 + extract 7 days (500 mg/kg p.o.); G4 = CCl4 + Legalon® 7 days (50 mg/kg p.o.), G5 = CCl4 + extract 21 days (500 mg/kg p.o.) e G6 = CCl4 + Legalon® 21 days (50 mg/kg p.o.)]. The hepatic oxidative injury was evaluated through biochemical parameters [alanine amino transferase (ALT), aspartate amino transferase (AST)] histopathological study, while thiobarbituric acid reactive products (TBAR), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were used to evaluate proantioxidant parameters. The plant extract tested was found effective as hepatoprotective as evidenced by a decreasing in the ALT and AST activities (p<0.001) and TBAR (plasma, p<0.001 and liver, p<0.001). Levels of GSH (blood, p<0.001 and liver, p<0.001) and antioxidant enzymes [CAT erythrocyte (p<0.05) and hepatic (p<0.01); SOD erythrocyte (p<0.001) and hepatic (p<0.001); GPx erythrocyte (p<0.001) and hepatic (p<0.001)] were also significantly increased. Histopathological changes induced by CCl4 were significantly reduced by the extract treatment. The data obtained were comparable to that of Legalon®, a reference hepatoprotective drug. The results showed that T. ulmifolia leaf extract protects against CCl4 induced oxidative damage. Therefore, this effect must be associated to its antioxidant activity, attributed to the phenolic compounds, present in these extract, which can act as free radical scavengers

Avaliação do status antioxidante, expressão gênica e polimorfismos dos genes SOD1, SOD2 e GPx1 em crianças, adolescentes e adultos jovens com diabetes tipo 1

Studies report that the pathophysiological mechanism of diabetes complications is associated with increased production of Reactive Oxygen Species (ROS)-induced by hyperglycemia and changes in the capacity the antioxidant defense system. In this sense, the aim of this study was to evaluate changes in the capacity of antioxidant defense system, by evaluating antioxidant status, gene expression and polymorphisms in the genes of GPx1, SOD1 and SOD2 in children, adolescents and young adults with type 1 diabetes. We studied 101 individuals with type 1 diabetes (T1D) and 106 normoglycemic individuals (NG) aged between 6 and 20 years. Individuals with type 1 diabetes were evaluated as a whole group and subdivided according to glycemic control in DM1G good glycemic control and DM1P poor glycemic control. Glycemic and metabolic control was evaluate by serum glucose, glycated hemoglobin, triglycerides, total cholesterol and fractions (HDL and LDL). Renal function was assessed by measurement of serum urea and creatinine and albumin-to-creatinine ratio (ACR) in spot urine. Antioxidant status was evaluate by content of reduced glutathione (GSH) in whole blood and the activity of erythrocyte enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also analyzed gene expression and gene polymorphisms of GPx1 (rs1050450), SOD1 (rs17881135) and SOD2 (rs4880) by the technique of real-time PCR (Taqman®). Most individuals with DM1 (70.3%) had poor glycemic control (glycated hemoglobin> 8%). Regarding the lipid profile, individuals with type 1 diabetes had significantly elevated total cholesterol (p <0.001) and LDL (p <0.000) compared to NG; for triglycerides only DM1NC group showed significant increase compared to NG. There was an increase in serum urea and RAC of individuals with DM1 compared to NG. Nine individuals with type 1 diabetes showed microalbuminuria (ACR> 30 mg / mg). There was a decrease in GSH content (p = 0.006) and increased erythrocyte GPx activity (p <0.001) and SOD (p <0.001) in DM1 group compared to NG. There was no significant difference in the expression of GPx1 (p = 0.305), SOD1 (.365) and SOD2 (0.385) between NG and DM1. The allele and genotype frequencies of the polymorphisms studied showed no statistically significant difference between the groups DM1 and NG. However, the GPx1 polymorphism showed the influence of erythrocyte enzyme activity. There was a decrease in GPx activity in individuals with type 1 diabetes who had a polymorphic variant T (p = 0.012). DM1 patients with the polymorphic variant G (AG + GG) for polymorphism of SOD2 (rs4880) showed an increase in the RAC (p <0.05). The combined data suggest that glucose control seems to be the predominant factor for the emergence of changes in lipid profile, renal function and antioxidant system, but the presence of the polymorphisms studied may partly contribute to the onset of complications

Capacidade antioxidante in vitro e avaliação da toxicidade aguda in vivo de extratos de folhas de Licania rígida Benth., Licania tomentosa (Benth.) Fritsch e Couepia impressa Prance (Chrysobalanaceae)

Licania rigida Benth., Licania tomentosa (Benth.) Fritsch, and Couepia impressa Prance (Chrysobalanaceae family) plants have long been used medicinally by the people from Northeastern Brazil. Crude extracts and infusions of these plants have been applied in the treatment of several conditions such as diabetes and rheumatism, degenerative diseases with involvement of reactive oxygen species (ROS). The aim of this study was to evaluate the aqueous, ethanolic, and hydroethanolic leaves extracts antioxidant capacity of these species, using several in vitro assay systems (reducing power, DPPH● scavenging, the β-carotene linoleate model system and lipid peroxidation inhibition in rat brain homogenate, using thiobarbituric acid reactive substances - TBARS). The oral acute toxicity of aqueous extracts was also evaluated in vivo. Results revealed that these extracts possess a potent reducing power and DPPH scavenging ability, as well as the ability to prevent TBARS formation in rat brain homogenate in a concentration-dependent manner. Regarding in vivo oral acute toxicity of the aqueous species extracts, no toxic effects were observed upon evaluating physiological, hematological and biochemical parameters. The presence of high levels of phenolics and flavonoids was determined mainly in the ethanol extract. However, the C. impressa hydroethanolic extract, fractionated with hexane, chloroform and ethyl acetate for analysis by NMR 1H, showed more efficient results than the reference antioxidant Carduus marianus. The classes of organics compounds were determined were phenolics in the fraction of ethyl acetate and terpenes in chloroform and hexane fractions. The ethil acetate fraction had the highest content of flavonoids and increased scavenging capacity of DPPH●, possibly by the presence of phenolic compounds. Therefore, a detailed investigation of the phytochemical composition and in vivo study of the C. impressa hydroethanolic extract is suggested to characterize the active compounds of the species

Efeitos da dieta suplementada com ômega-3 no músculo sóleo de ratos submetidos à natação: análise histológica e morfométrica

As lesões musculares têm sido observadas como as mais frequentes nos esportes. Considerando a produção de espécies reativas de oxigênio como um fator de risco para instalação de lesões e características antioxidantes e anti-inflamatórias do ômega-3, o objetivo deste trabalho foi verificar as alterações histológicas e morfométricas do músculo sóleo de ratos que realizaram natação, associado a uma dieta suplementada com ômega-3. Para sua realização foram utilizados 31 ratos Wistar divididos em quatro grupos, sendo os grupos A e C suplementados com azeite de oliva e B e D com 3g/dia de ômega-3 por quatro semanas. Os grupos C e D foram submetidos à natação cinco dias/semana por 28 dias, com acréscimo de 5% do peso corporal a partir da segunda semana, enquanto que os grupos A e B não realizaram treinamento. Após este período os animais foram sacrificados, o músculo sóleo retirado e corado com Hematoxilina-eosina para avaliação morfológica. Análise de variância bifatorial, com nível de significância de 5%, foi utilizada para análise dos valores do menor diâmetro das fibras musculares. Os grupos A e B (sedentários) apresentaram padrões histológicos de normalidade. O grupo C apresentou aumento do tecido endomisial e do número de núcleos, presença de fibras fagocitadas e de contornos poligonais não mantidos, enquanto que o grupo D apresentou poucas fibras fagocitadas e de contornos poligonais preservados. Com relação à medida do menor diâmetro das fibras musculares, as análises mostraram diferenças para o fator treinamento, mas não para o fator suplementação e a interação entre eles. As alterações histológicas induzidas pelo exercício foram atenuadas no grupo suplementado com ômega-3, sugerindo um efeito protetor da suplementação, contudo, o aumento do diâmetro das fibras para os grupos expostos ao exercício está relacionado ao efeito do treinamento e não à suplementação.

Metabolismo mitocondrial, radicais livres e envelhecimento

O envelhecimento pode estar associado ao maior acúmulo de lesões celulares decorrentes das espécies reativas do oxigênio e do nitrogênio derivadas do metabolismo mitocondrial. Com a progressão da idade, há acúmulo de proteínas, lipídeos, carboidratos e DNA oxidados em relação a organismos jovens, de acordo com a teoria dos radicais livres. Entretanto, nem sempre os idosos ou animais envelhecidos apresentam maior estresse oxidativo que os jovens. Este artigo discute o paradoxo da teoria dos radicais livres de acordo com a teoria da biogênese da manutenção adequada do metabolismo mitocondrial. Diversos fatores podem contribuir para a redução do estresse oxidativo, como a hormese induzida pela prática regular de exercícios físicos, a restrição calórica, a ingestão de antioxidantes nutricionais e o aumento da produção de antioxidantes celulares que. em conjunto, estes promovem a expressão das sirtuínas e das proteínas do choque térmico, protegendo a integridade e funcionalidade mitocondriais, reduzindo o estresse oxidativo e nitrosativo, o que está associado à redução do envelhecimento e aumento da longevidade.

Morphological and physiological alterations induced by lactofen in soybean leaves are reduced with nitric oxide

O lactofen é um herbicida difeniléter recomendado para controlar plantas daninhas de folhas largas em campos de soja (Glycine max) e seu mecanismo de ação é a inibição da protoporfirinogênio-IX oxidase (Protox), que atua na biossíntese de clorofilas. Essa inibição resulta em um acúmulo de protoporfirina-IX, o que leva à produção de espécies reativas de oxigênio (ROS), causando estresse oxidativo. Conseqüentemente, podem ocorrer manchas, enrugamento e queima das folhas, o que leva à paralisação temporária do crescimento da cultura. Porém, o óxido nítrico (NO) atua como um antioxidante na eliminação direta das ROS. Assim, o objetivo deste trabalho foi verificar, por meio de avaliações fitométricas e bioquímicas, o efeito protetor do NO em plantas de soja tratadas com o herbicida lactofen. Plantas de soja foram pré-tratadas com diferentes doses de Nitroprussiato de Sódio (SNP), substância doadora de NO, e então pulverizadas com 168 g a.i. ha-1 lactofen. O pré-tratamento com SNP foi benéfico, pois o NO reduziu os sintomas de injúria causados pelo lactofen nos folíolos jovens e manteve baixos teores de açúcares solúveis. Porém, o NO proporcionou crescimento mais lento das plantas. Desta forma, posteriores estudos são necessários para elucidar os mecanismos de ação do NO na sinalização do estresse promovido pelo lactofen na cultura da soja.

Análise de polimorfismos dos genes da rota quinureniana em pacientes com meningite bacteriana.

Bacterial meningitis (BM) is still an important infectious disease causing death and disability. Invasive bacterial infections of the central nervous systems (CNS) generate some of the most powerful inflammatory responses known, which contributes to neuronal damage. The DNA microarray technology showed alterations in the kynurenine (KYN) pathway that is induced in BM and other diseases associated with inflammation, leading to brain injury. Our main aim was to search SNPs previously described in the KYN path enzymes to investigate a putative association of this SNPs with imbalanced in this pathway in patients with BM. The patients included in this study were 33 males and 24 females, with ages varying from 02 months to 68 years. SNPs were located inside of the domain conserved in KYNU, IDO, KATI and KATII. Primers were designed for analysis of SNPs already described by PIRA-PCR followed by RFLP. The analysis of KYNU+715G/A SNP found a heterozygous frequency of 0.033. We did not found the variant allele of SNP KYNU+693G/A, KATI+164T/C, KATII+650C/T and IDO+434T/G. Despite of previews studies showing the importance of KYN pathway we did not found one association of these SNPs analyzed with susceptibility or severity of MB in study population.

Associação entre polimorfismos em enzimas de reparo de DNA e ocorrência de meningite bacteriana.

Despite advances in vaccine development and therapy, bacterial meningitis (BM) remains a major cause of death and long-term neurological disabilities. As part of the host inflammatory response to the invading pathogen, factors such as reactive oxygen species are generated, which may damage DNA and trigger the overactivation of DNA repair mechanisms. It is conceivable that the individual susceptibility and outcome of BM may be in part determined by non synonymous polymorphisms that may alter the function of crucial BER DNA repair enzymes as PARP-1, OGG-1 and APE-1. These enzymes, in addition to their important DNA repair function, also perform role of inflammatory regulators. In this work was investigated the non synonymous SNPs APE-1 Asn148Glu, OGG-1 Ser326Cys,PARP-1 Val762Ala, PARP-1 Pro882Leu and PARP-1 Cys908Tyr in patients with bacterial meningitis (BM), chronic meningitis (CM), aseptic meningitis (AM) and not infected (controls). As results we found increased frequency of variant alleles of PARP-1 Val762Ala (P = 0.005) and APE-1 Asn148Glu (P=0.018) in BM patients, APE-1 Asn148Glu in AM patients (P = 0.012) and decrease in the frequency of the variant allele OGG-1 Ser326Cys in patients with CM (P = 0.013), regarding the allelic frequencies in the controls. A major incidence of individuals heterozygous and/ or polymorphic homozygous in BM for PARP-1 Val762Ala (P= 0.0399, OD 4.2, 95% IC 1.213 -14.545) and PARP-1 Val762Ala/ APE-1 Asn148Glu (P = 0.0238, OD 11.111, 95% IC 1.274 - 96.914) was observed related to what was expected in a not infected population. It was also observed a major incidence of combined SNPs in the BM patients compared with the control group (P=0.0281), giving evidences that SNPs can cause some susceptibility to the disease. This combined effect of SNPs seems to regulate the principal cytokines and other factors related to BM inflammatory response and point the importance of DNA repair not only to repair activity when DNA is damaged, but to others essential functions to human organism balance.

Análise das mudanças no perfil protéico durante o estresse oxidativo in vivo e atuação da MutY-Glicosilase em respostas celulares

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Composição ictiofaunística e estratégias reprodutivas de quatro espécies de peixes nativos da Bacia Hidrográfica Piranhas - Assu, Rio Grande do Norte

This study focuses on the fish fauna composition and reproductive strategies of four native fish species in relation to environmental variables of the Piranhas-Assu hydrographic basin of the Caatinga biome, Rio Grande do Norte, Brazil. Fish and environmental data were collected monthly during the period September 2008 to February 2010, in the Marechal Dutra reservoir and River Acauã a tributary of Piranhas- Assu. The fish were measured, weighed and dissected, and the gonads were removed, weighed and examined macroscopically for identification and determination of gonad maturation stages. The results of this work generated seven articles. The first article is about the fish fauna composition of the Piranhas-Assu hydrographic basin, Rio Grande do Norte. The 602 fish samples captured were distributed in four orders (Characiformes, Perciformes, Siluriformes and Synbranchiformes), 11 families and 22 species, of which 17 are endemic to the Caatinga ecoregion. The order Characiformes was more representative followed by Perciformes, Siluriformes and Synbranchiformes. The second article is about the length-weight relationship and growth of seven native fish species Crenicichla menezesi, Cichlasoma orientale, Triportheus angulatus, Psectrogaster rhomboides, Pimelodella gracilis, Prochilodus brevis and Leporinus piau from a semiarid Brazilian reservoir. The third article is about the reproductive aspects of Crenicichla menezesi. Males were larger, heavier and with a slight predominance as compared to females. Four stages of gonadal development were characterized, being immature, maturing, mature and spent. The females reached sexual maturity earlier than males, with an average fecundity of 398 oocytes per batch. The spawning was partial with a long reproductive period. The fourth article deals with the reproductive strategy of Leporinus piau a neotropical freshwater fish in semi-arid region of Brazil. The population of L. piau (n = 211) showed a slight predominance of males (55%), with larger and heavier females. The males matured earlier than the females. This species presented total spawning, with an average fecundity of 55,000 mature oocytes. Rainfall and concentration of dissolved oxygen acted as influential factors during the spawning season. L. piau shows a seasonal reproductive strategy. The fifth article is related to the morphometric-meristic characteristics and reproductive aspects of freshwater sardine, Triportheus angulatus from River Acauã of the Caatinga biome. There was a predominance of larger females, reaching first maturation before males. There was total spawning during the rainy period of the region. The sixth article reports on the reproductive strategy of Psectrogaster rhomboides. The sex ratio was 1M: 1F, with negative allometric growth. Males reached sexual maturity earlier than females Females and males showed four stages of gonadal development and spawned during the rainy season. The fecundity was low and this species presented total spawning. The seventh article reports on the dynamics of territorial behavior of Crenicichla menezesi. Ten agonistic behaviors displayed by the males were observed: frontal and lateral threat, chasing, circular chasing, perpendicular, lateral and mouth attacks, escape, parallel positioning and stationary. The formation of four social groups was observed among males: without interaction; interaction with submission and escape; with frontal and lateral agonistic interactions. In social interactions between males and females, it was observed that the larger males interacted more among themselves and with the larger females. The large male established its territory and the two small males along with the small female were excluded from the other groups. These studies clarified the fish fauna composition and reproductive strategies of four native species Crenicichla menezesi, Leporinus piau, Triportheus angulatus and Psectrogaster rhomboides of the Piranhas- Assu hydrographic basin of the Caatinga biome, Rio Grande do Norte, Brazil.

Comprovação do efeito antioxidante de plantas medicinais utilizadas no tratamento do Diabetes mellitus em animais: artigo de atualização

Diabetes mellitus (DM) é uma síndrome de etiologia múltipla caracterizada por hiperglicemia crônica. Esta hiperglicemia induz o aumento na produção de espécies reativas de oxigênio (ERO) e diminuição das defesas antioxidantes. Devido às complicações causadas pelo diabete, muitos indivíduos optam por terapias alternativas à base de plantas medicinais para amenizar seus efeitos. Sendo assim, nesta revisão de literatura, foram analisados e descritos diversos trabalhos experimentais com a utilização de animais diabéticos para comprovar os efeitos antioxidantes de algumas dessas plantas e verificar se os títulos e resumos disponibilizados nos artigos são compatíveis aos objetivos de nossa busca.

Biopatologia do Helicobacter pylori

A infecção pelo Helicobacter pylori (H. pylori) induz inflamação persistente na mucosa gástrica com diferentes lesões orgânicas em humanos, tais como gastrite crônica, úlcera péptica e câncer gástrico. Os fatores determinantes desses diferentes resultados incluem a intensidade e a distribuição da inflamação induzida pelo H. pylori na mucosa gástrica. Evidências recentes demonstram que cepas do H. pylori apresentam diversidade genotípica, cujos produtos acionam o processo inflamatório por meio de mediadores e citocinas, que podem levar a diferentes graus de resposta inflamatória do hospedeiro, resultando em diferentes destinos patológicos. Cepas H. pylori com a ilha de patogenicidade cag induzem resposta inflamatória mais grave, através da ativação da transcrição de genes, aumentando o risco para desenvolvimento de úlcera péptica e câncer gástrico. O estresse oxidativo e nitrosativo induzido pela inflamação desempenha importante papel na carcinogênese gástrica como mediador da formação ou ativação de cancerígenos, danos no DNA, bem como de alterações da proliferação celular e da apoptose.