Vitamin C partially attenuates male reproductive deficits in hyperglycemic rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Ginkgo biloba on the reproductive outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats

The aim of the present study was to evaluate the effect of Ginkgo biloba treatment (EGb 761, 200 mg kg-1 day-1) administered from day 0 to 20 of pregnancy on maternal reproductive performance and on the maternal and fetal liver antioxidant systems of streptozotocin-induced diabetic Wistar rats. on day 21 of pregnancy, the adult rats (weighing approximately 250 ± 50 g, minimum number = 13/group) were anesthetized to obtain maternal and fetal liver samples for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total glutathione (GSH-t) determinations. The uterus was weighed with its contents. The diabetic (G3) and treated diabetic (G4) groups of rats presented significant maternal hyperglycemia, reduced term pregnancy rate, impaired maternal reproductive outcome and fetal-placental development, decreased GSH-Px (G3 = G4 = 0.6 ± 0.2) and SOD (G3 = 223.0 ± 84.7; G4 = 146.1 ± 40.8), and decreased fetal CAT activity (G3 = 22.4 ± 10.6; G4 = 34.4 ± 14.1) and GSH-t (G3 = G4 = 0.3 ± 0.2), compared to the non-diabetic groups (G1, untreated control; G2, treated). For G1, maternal GSH-Px = 0.9 ± 0.2 and SOD = 274.1 ± 80.3; fetal CAT = 92.6 ± 82.7 and GSH-t = 0.6 ± 0.5. For G2, G. biloba treatment caused no toxicity and did not modify maternal or fetal-placental data. EGb 761 at the nontoxic dose used (200 mg kg-1 day-1), failed to modify the diabetes-associated increase in maternal glycemia, decrease in pregnancy rate, decrease in antioxidant enzymes, and impaired fetal development when the rats were treated throughout pregnancy (21 days).

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

INTRODUÇÃO: Modelos experimentais são desenvolvidos com propósito de ampliar o entendimento dos mecanismos fisiopatológicos envolvidos no diabete. Os achados experimentais levam ao desenvolvimento de tratamentos alternativos para a manutenção das condições metabólicas normais. Existem vários estudos sobre o diabete induzido por streptozotocin mimetizando o quadro clínico do DM2. No entanto, a interação entre os níveis de glicose, perfil lipídico e estresse oxidativo nestes animais são escassos. Portanto, o objetivo do trabalho foi avaliar estes parâmetros em ratas Wistar adultas com diabete induzido com streptozotocin no período neonatal. MÉTODOS: Fêmeas recém-nascidas receberam streptozotocin (70mg/Kg, ip) no 5º dia de vida (n5-STZ). A glicemia foi medida no terceiro e quarto meses de vida dos animais. No final do quarto mês de vida, amostras de sangue foram coletadas e processadas para a dosagem de lipídios e marcadores de estresse oxidativo. RESULTADOS: A glicemia das ratas do grupo n5-STZ foi significativamente maior comparada às ratas do grupo controle (p<0,05). Não houve alteração nos níveis de colesterol total e triglicérides, peroxidação lipídica (TBARS), atividade da SOD e determinação da GSH-t (p>0,05) nas ratas n5-STZ em relação às ratas do grupo controle. No entanto, houve diminuição significativa no HDL-colesterol (p<0,05). CONCLUSÃO: Este modelo de indução de diabete em ratas causou hiperglicemia (120-360mg/dL), caracterizando o diabete moderado. Essa glicemia levou a alterações no HDL-colesterol, a qual não foi suficiente para prejudicar a atividade das enzimas antioxidantes ou marcadores da peroxidação lipídica na vida adulta. Além disso, esta investigação experimental contribuiu para entender os diferentes resultados encontrados em outros modelos deindução do diabete moderado em animais de laboratório, como também para a melhor compreensão dos mecanismos fisiopatológicos do diabete moderado ou da hiperglicemia em humanos.

Diabetes induced immunological and biochemical changes in human colostrum

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids

OBJECTIVE: the potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress.METHODS:, Nine patients (seven female and two male; me. an age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation, both induced by tert butyl hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant status was assayed by total plasma antioxidant capacity (TRAP) and microsomal lipid peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase erythrocyte enzymatic activities were also determined.RESULTS: No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores, with the exception of erythrocyte sedimentation rate, which decreased with both treatments. Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels, increased chemiluminescence induced by t-BuOOH, and higher SOD activity in patients with UC. Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid peroxidation, and catalase were not different from those in the control group.CONCLUSIONS: the results indicated that plasma oxidative stress occurs in patients with UC, and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids. However, there was no improvement in most laboratory indicators, sigmoidoscopy, and histology scores. The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress. (C)Elsevier B.V. 2003.

Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental paracoccidioidomycosis in the mouse. III. Histopathological and immunological findings after intravenous infection in the presence or absence of previous immunization

Cinqüenta camundongos suíços, brancos, com quatro semanas de idade, foram inoculados com 5x10(5) formas leveduriformes, viáveis de Paracoccidiodes brasiliensis (cepa 18). Dez destes animais tinham sido previamente imunizados com antígeno particulado de P. brasiliensis, durante quatro semanas, por injeção intradérmica. Os controles consistiram de 10 animais que foram somente imunizados e 10 inoculados com solução salina estéril. Os animais foram sacrificados após 2, 4, 7, 11 e 16 semanas. Estudamos: 1) resposta de hipersensibilidade retardada medida pelo teste do coxim plantar, 24 horas antes do sacrifício; 2) anticorpo- gênese específica avaliada pelo teste de imunodifusão dupla em gel de ágar; 3) histopatologia dos pulmões, fígado, baço, supra-renal e rins. Observamos: 1) os animais imunizados desenvolveram resposta imunecelular mais intensa que os infectados; 2) a infecção deprimiu a resposta imunecelular dos animais imunizados; 3) a histopatologia da infecção endovenosa revelou inflamação granulomatosa sistêmica e progressiva. Os animais infectados após imunização prévia apresentaram inflamação pulmonar menos extensa, com granulomas menores e com reduzido número de fungos. O presente modelo murino de paracoccidioidomicose mimetiza alguns achados da forma humana subaguda da micose (doença sistêmica com depressão da imunidade celular). O esquema de imunização extrapulmonar utilizado foi capaz de induzir certo grau de proteção do pulmão contra um desafio infeccioso pelo P. brasiliensis.

Short Implant to Support Maxillary Restorations: Bone Stress Analysis Using Regular and Switching Platform

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antioxidant defense in rat brain regions after developmental lead exposure

Oxidative stress is considered a possible molecular mechanism involved in Pb neurotoxicity. Considering the vulnerability of the developing brain to Pb neurotoxicity, this study was carried out to investigate the effects of low-level developmental Pb exposure on brain regions antioxidant enzymes activities. Wister dams were exposed to 500 ppm of Pb, as Pb acetate, or to 660 ppm Na acetate in the drinking water during pregnancy and lactation. The activities of superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase were determined in the hypothalamus, hippocampus and striatum of male pups at 23 (weaned) or 70 days (adult) of age. In the Pb-exposed 23-day-old pups, the activity of SOD was decreased in the hypothalamus. Regarding adults, there was no significant treatment effect in any of the enzymes and regions evaluated. Based on the present results, it seems that oxidative stress due to decreased antioxidant function may occur in weaned rats but it is suggested that this should not be the main mechanism involved in the neurotoxicity of low-level Pb exposure. (C) 2001 Elsevier B.V. Ireland Ltd. All rights reserved.

Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nitric oxide reduces oxidative stress generated by lactofen in soybean plants

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Can a Strychnos species be used as antiulcer agent? Ulcer healing action from alkaloid fraction of Strychnos pseudoquina St. Hil. (Loganiaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antioxidant activity of indigo and its preventive effect against ethanol-induced DNA damage in rat gastric mucosa

Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, p. o.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, p.o.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.

Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)