Made available in DSpace on 2015-03-26T13:36:35Z (GMT). No. of bitstreams: 1 texto completo.pdf: 318019 bytes, checksum: f14201c1f1fe349bcc7b8771be868f8e (MD5) Previous issue date: 2006-02-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The effects of aluminum on growth, respiratory activities and on some enzymes related to reactive oxygen species (ROS) elimination were examined in roots of two corn seedlings cultivated in nutrient solution, by comparing a susceptible (BR 106) and a tolerant cultivar (BR 206). Growth of the main root decreased in both cultivars, mainly in the susceptible one, at aluminum concentration of 50 and 100 µM. Only in the tolerant cultivar aluminum induced a decrease in the leak of electrolytes. On the contrary, the susceptible cultivar showed significant increase in lipid peroxidation. Aluminum promoted higher activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX), only in the tolerant cultivar. No difference was observed in the activities of catalase (CAT), peroxidases (POX) and glutathione reductase (GR) in both cultivars. Ascorbate content was not altered, but the ascorbate redox state (ratio ascorbate/dehydroascorbate) increased in the tolerant cultivar. In absence of aluminum, respiratory oxygen consumption was higher in the tolerant cultivar, both in states 3 and 4. These respiratory activities were decreased by aluminum in the susceptible cultivar, but were increased in the tolerant one. ADP/O ratios were decreased by aluminum, in both cultivars at a similar extent. The cytochrome c pathway was not altered by aluminum in the tolerant cultivar, but decreased in the susceptible one. Without aluminum, the susceptible cultivar showed a higher alternative oxidase (AOX) activity than the tolerant one. Aluminum promoted a decrease in AOX activity in the susceptible cultivar, the opposite response being observed in the tolerant one. In both cultivars aluminum induced an increase above 120% in the residual oxygen consumption. Activity of the plant uncoupling mitochondrial protein (PUMP) was decreased by aluminum in the susceptible cultivar and enhanced in the tolerant one. These results suggest that the tolerant cultivar possesses a more efficient enzymatic system for ROS removal than the sensitive one. Furthermore, the partial mitochondrial uncoupling, resulting from higher AOX and PUMP activities should have contributed to the higher aluminum stress tolerance showed by cultivar BR 206. / Os efeitos do alumínio sobre o crescimento, a respiração e as atividades de algumas enzimas envolvidas na eliminação de espécies reativas de oxigênio foram avaliadas em plântulas de duas cultivares de milho, uma sensível (BR 106) e outra tolerante ao alumínio (BR 206), cultivadas em solução nutritiva, pH 4,0. O alumínio, nas concentrações de 50 e 100 µM, reduziu o crescimento da raiz principal das duas cultivares, especialmente da cultivar sensível. O alumínio reduziu o extravasamento de eletrólitos, apenas nas raízes da cultivar tolerante e aumentou a peroxidação de lipídios, apenas na cultivar sensível. O tratamento com alumínio resultou em aumentos significativos nas atividades da dismutase do superóxido (SOD) e da peroxidase do ascorbato (APX), apenas na cultivar tolerante. Entretanto, não foram observadas diferenças significativas nas atividades da catalase (CAT), das peroxidades (POX) e da redutase da glutationa (GR), em ambas as cultivares. Os teores de ascorbato também não apresentaram variação significativa, mas foi observado aumento no estado redox (razão ascorbato/desidroascorbato), porém apenas na cultivar tolerante. No tratamento controle, as taxas respiratórias de mitocôndrias isoladas da cultivar tolerante se apresentaram mais elevadas, tanto no estado 3 como no estado 4. Estas taxas foram reduzidas pelo alumínio na cultivar sensível, e aumentadas na cultivar tolerante. As razões ADP/O foram reduzidas pelo tratamento com alumínio, nas duas cultivares, na mesma proporção. A rota do citocromo c não foi alterada pelo alumínio, na cultivar tolerante, mas foi reduzida na cultivar sensível. Na ausência de alumínio, a cultivar sensível apresentou atividade da oxidase alternativa (AOX) mais elevada, que foi reduzida pela presença de alumínio. Ao contrário, o consumo de oxigênio pela rota alternativa foi aumentado, pelo alumínio, na cultivar tolerante. Nas duas cultivares, o alumínio promoveu acréscimos superiores a 120% no consumo residual de oxigênio. A atividade da proteína desacopladora de plantas (PUMP) foi diminuída pelo alumínio, na cultivar sensível, e aumentada, na tolerante. Estes resultados sugerem que a cultivar tolerante possua um mecanismo enzimático mais eficiente de remoção ou neutralização de espécies reativas de oxigênio que a cultivar sensível. Além disso, o parcial desacoplamento mitocondrial observado, resultante do aumento das atividades da oxidase alternativa e da proteína desacopladora, deve contribuir para a maior tolerância da cultivar BR 206 ao estresse por alumínio.

L’objectif de notre travail consiste à caractériser des nanoparticules d’oxyde de fer (Fe3O4) et étudier leur toxicité aiguë chez le rat Wistar. Nos résultats ont montré que l’administration orale aiguë des Fe3O4, entraîne une altération dose- et temps-dépendante des paramètres du stress oxydant ainsi qu’une atteinte hépatique. En ce qui concerne l’étude in vitro sur des mitochondries isolées, nos résultats ont montré que ces nanoparticules n’altèrent ni les différents complexes de la chaîne respiratoire mitochondriale ni le couplage mitochondrial, et ceci dans aucun des organes étudiés (cerveau, cœur, poumon, foie et reins) et quelle que soit la concentration utilisée (100, 200, 300 et 500 μg/ml), alors que les mitochondries hépatiques isolées des rats âgés (18 mois), une altération est observée au niveau de tous les complexes de la chaîne respiratoire mitochondriale hépatique ainsi que pour le couplage mitochondrial quelle que soit la concentration utilisée (250, 300 et 350 μg/ml) alors que pour les rats jeunes (3mois) on n’observe aucune altération. / The objective of our work is to characterize iron oxide nanoparticles (Fe3O4) and study their acute toxicity in Wistar rats. Our results showed that acute oral administration of Fe3O4, results in a dose and time-dependent alteration of oxidative stress parameters as well as liver damage. Regarding the in vitro study on isolated mitochondria, our results showed that these nanoparticles do not adversely affect the various complexes of the mitochondrial respiratory chain or mitochondrial coupling in any of the organs studied (brain, heart, lung, liverand kidneys) and regardless of the concentration used (100, 200, 300 and 500 μg/ml) while the isolated liver mitochondria from aged rats (18 months), an alteration is observed at all the complexes of the liver mitochondrial respiratory chain as well as the mitochondrial coupling regardless of the concentration used (250, 300 and 350 μg/ml), whereas for the young rats (3 months) no change is observed.

Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.