Intake of isoflavone-supplemented soy yogurt fermented with Enterococcus faecium lowers serum total cholesterol and non-HDL cholesterol of hypercholesterolemic rats

The aim of this study was to obtain an isoflavone-supplemented soy yogurt, fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus ssp jugurti, with suitable sensory properties and to assess the effects of the final product on blood lipids in hypercholesterolemic rats. Four isoflavone supplementation procedures were tested, in which the isoflavone was added at these stages: (1) before heat-treatment; (2) after heating and before fermentation; (3) after fermentation and (4) in the okara (by-product of soy milk) flour stirred into the fermented product when consumed. The products were subjected to a test of sensory acceptability. To assess their potential hypocholesterolemic properties in vivo, four groups of rats were used: control (C), hypercholesterolemic (H), hypercholesterolemic plus fermented product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented product (HFI). Hypercholesterolemia was induced in rats of groups H, HF and HFI by feeding them on a commercial rat chow to which cholesterol and cholic acid had been added. Total, HDL and non-HDL cholesterol and triglycerides were measured in the blood of the rats. No significant sensorial differences were detected among the samples of soy yogurt supplemented with isoflavones at various processing stages. Rats fed a fermented soy product enriched with isoflavones (HFI group) had significantly (P < 0.05) less serum total cholesterol (15.5%) compared with rats fed a hypercholesterolemic diet (H group). Non-HDL cholesterol was less (P < 0.05) in rats fed a fermented soy product enriched or not with isoflavones (27.4 and 23.2%) compared to H group. The HDL-C and triglyceride concentrations did not differ significantly among the groups. It was possible to obtain an isoflavone-supplemented soy yogurt with satisfactory sensory characteristics. The resulting supplemented soy yogurt was capable of producing a lipid-lowering effect in hypercholesterolemic rats, relative to the animals that did not consume this product.

beta-Conglycinin (7S) and glycinin (11S) exert a hypocholesterolemic effect comparable to that of fenofibrate in rats fed a high-cholesterol diet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats

The antioxidant activity of the amino acid glutamine was investigated to obtain protection against peroxidative damage in rat kidney and nephrotoxicity induced by the treatment with a single dose of the antitumoral cisplatin (5 mg kg(-1) body weight). The animals were divided into four treatment and control groups of six rats each (n = 6). Cisplatin was injected i.p. and glutamine (300 mg kg(-1) body weight) was given by gavage 24 h before the cisplatin injection. After 24 h and 7 days of cisplatin administration, the rats were sacrificed. A single dose of cisplatin resulted in significant reduction in body weight and creatinine clearance, and higher urinary volumes were observed in all groups treated with this antitumor drug (P < 0.05). Renal tissue from cisplatin-treated rats showed an increase in malondialdehyde production and increase in glutathione contents 24 h and 7 days after cisplatin administration. Pretreatment of rats with glutamine substantially inhibited the increase in the levels of renal glutathione induced by cisplatin 24 h after the i.p. injection. The malondialdehyde, in the renal tissues was significantly reduced 7 days after cisplatin treatment. However, the reduction in the peroxidative damage did not reach the value of the control group. The protective effects obtained by glutamine pretreatment in peroxidative alterations were not observed in the other parameters studied. These results suggest that glutamine partially protect against cisplatin-induced lipid peroxidation damage, but it was not enough to inhibit cisplatin-induced nephrotoxicity in rats. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

The effect of pyrazinamide and rifampicin on isoniazid metabolism in rats

Hepatotoxicity is the main concern during tuberculosis chemotherapy with the first-line drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR). Since these hepatotoxic events have been associated with INH metabolites, the study aimed to measure the area under curve (AUC) parameter for INH and its metabolites acetylisoniazid (AcINH), hydrazine (Hz) and acetylhydrazine (AcHz), when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg + RMP 100 mg; INH 100 mg + PYR 350 mg; INH 100 mg + PYR 350 mg + RMP 100 mg. It was found that co-administration of RMP, PYR and RMP + PYR caused a significant decrease in the AUC for INH. Co-administration of PYR was the only treatment that caused a significant increase in the AUC for Hz and a decrease in the AUC for its acetylated product AcHz. The AUC for AcINH was not significantly altered in any experimental group. In conclusion, the increased metabolism of INH in all the drug combinations and the significantly higher production of Hz in the group INH + PYR might be linked with exacerbated hepatotoxic effects of these drug associations. Copyright (c) 2007 John Wiley & Sons, Ltd.

The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats

Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg + RMP 100 mg; INH 100 mg + PYR 350 mg; INH 100 mg + PYR 350 mg + RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V-d/F), half-life of elimination t(1)/2(beta)) and clearance (Cl-T/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl-T/F and a decrease in the AUC. The combination INH + PYR + RMP caused an increase in the Cl-T/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects. Copyright 0( 2007 John Wiley & Sons, Ltd.

Effects of pancreas transplantation on oxidative stress in pulmonary tissue from alloxan-induced diabetic rats

Purpose. There is considerable evidence that cellular oxidative stress caused by hyperglycemia plays an important role in the genesis and evolution of chronic diabetic lesions. In this study, we determined the effectiveness of pancreas transplantation (PT) in preventing the imbalance caused by excessive production of reactive oxygen species over antioxidant defenses in lungs of rats rendered diabetic by alloxan injection.Methods. Sixty inbred male Lewis rats, weighing 250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats.Results. The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). They also showed significantly increased LPO concentrations in the lungs (P < .01) after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant activities were significantly reduced in these periods (P < .01) 12 weeks after diabetes induction. Successful PT corrected all clinical and metabolic changes in the diabetic rats, with sustained normoglycemia throughout the study. Excessive lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were already back to normal 4 weeks after PT.Conclusion. PT can control oxidative stress in pulmonary tissue of diabetic rats. It may be the basis for preventing chronic diabetic lesions in lungs.

Carcinogenesis of the upper gastrointestinal tract induced by N-methyl-N '-nitro-nitrosoguanidine and reflux of duodenal contents in the rat

Purpose: To investigate the combined effects of reflux of duodenal contents through the pylorus and treatment with N-methyl-N'-nitro-nitrosoguanidine ( MNNG) on the development of lesions in the glandular stomach, at the gastrojejunal anastomosis and in the forestomach of rats. Methods: Eighty Male Wistar rats were divided into 4 groups: G1: MNNG + Reflux, G2: Reflux, G3: MNNG and G4: Gastrostomy. MNNG was given in the drinking water ( 100 mg/ml) for 12 weeks and then two groups ( G1 and G2) were submitted to a gastrojejunal anastomosis followed by section of the afferent loop and suture of both stumps to allow reflux of duodenal contents through the pylorus. The animals were sacrificed 18 and 36 weeks after surgery. The lesions obtained in the antral mucosa, at the gastrojejunal anastomosis and in the forestomach were analysed histologically. Results: Duodenal reflux induced proliferative lesions at both glandular and squamous mucosa of the stomach. In the antrum, adenomatous hyperplasia (AH) was observed in 20% and 50% of the animals at the 18(th) and 36(th) weeks respectively. Aditionally 85% of the animals presented AH at the gastrojejunal anastomosis and 60% developed squamous hyperplasia at the squamous portion of the stomach. MNNG treatment plus duodenal reflux enhanced the development of malignant tumors at both glandular and squamous mucosa, since there were 30% of antral adenocarcinomas and 45% of squamous carcinomas at the 18th week and the frequency of these malignant tumors rose to 50% in the antrum and 65% in the squamous mucosa at the 36th week. Conclusion: The reflux of duodenal contents through the pylorus enhanced the development of proliferative lesions, benign and malignant, in the glandular stomach and in the forestomach of rats.

Alterations in the intestinal wall due to protein malnutrition in rats. Evaluation of the rupture strength and the tissue's collagen

OBJETIVO: Avaliar o efeito da desnutrição protéica na parede intestinal do rato através da medida de força de ruptura e dosagem do colágeno tecidual no íleo e cólon distal. MÉTODOS: Foram utilizados 120 ratos, pesando em média 100g, que receberam durante 07 dias uma dieta padrão, contendo 20% de caseína para adaptação dos animais as condições do biotério. Após esse período os animais foram divididos em dois grupos de 60, o controle denominado grupo um que recebeu a dieta padrão, e o grupo teste denominado grupo dois, que recebeu dieta hipoprotéica contendo 2% de caseína. Os dois grupos receberam suas respectivas dietas por um período de 21 dias. Após esse período iniciou-se o sacrifício seqüencial dos animais em ambos os grupos, em número de 12 animais em cada momento, correspondendo ao dia Zero (MO), 4º dia (M1), 7º dia (M2), 14º dia (M3), e 21º dia (M4) sendo mantida a mesma dieta até o final do sacrifício. em cada momento foram avaliados o peso corpóreo, albumina sanguínea, hidroxiprolina tecidual, relação hidroxiprolina/proteína tecidual e a força de ruptura no segmento ileal e cólico dos animais. RESULTADOS: Observou-se que a força de ruptura do segmento ileal e do cólon distal foi menor nos animais desnutridos (Grupo 2). A perda da resistência mecânica foi maior no segmento do cólon distal do que no segmento ileal, provavelmente pela menor concentração do colágeno tecidual no cólon distal. CONCLUSÃO: A desnutrição protéica induz a diminuição da resistência mecânica no íleo e no cólon distal associado a diminuição do colágeno tecidual na parede intestinal.

Pancreas transplantation prevents cellular oxidative stress in kidneys of alloxan-induced diabetic rats

Purpose. Oxidative stress is one of the most important mechanisms to explain genesis of the complications in the chronic progression of diabetes. In this investigation we studied the effects of pancreas transplantation (PT) on the imbalance caused by excessive production of free oxygen radicals by antioxidant defenses of rats with serious chronic hyperglycemia induced by alloxan.Methods. Ninety inbred male Lewis rats were randomly distributed into three groups: NC-30 nondiabetic controls; DC-30 diabetic controls without any treatment; PT-30 diabetic rats undergoing syngeneic PT from normal donor Lewis rats. Each experimental group was then split into three subgroups of 10 animals for sacrifice after 1, 3, or 6 months. Clinical and laboratory parameters from all rats as well as lipid hydroperoxide (LPO) concentrations and renal tissue enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were recorded for all rats.Results. Successful PT corrected clinical and laboratory alterations in diabetic rats with sustained normoglycemia throughout the study. A significant increase in LPO concentration and a marked reduction in SOD and CAT enzyme activity were observed in DC rats; there was no significant variation in renal tissue GSH-Px in this group. However, alterations in DC rats were completely restored from 1st month after PT; all evaluated enzyme levels did not significantly differ (P < .01) from those in NC controls.Conclusion. Successful PT controlled cellular oxidative stress in diabetic kidneys, which may prevent chronic lesions.

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).

Anxiolytic effect of Rubus brasilensis in rats and mice

The aim of the present work was to investigate if infuse and ethanolic extracts (aqueous, butanolic and wax fractions) of Rubus brasiliensis Martius (Rosaceae) induce anxiolytic effect. The extracts were administered to male Wistar rats and Swiss mice per oral route, at 50, 100 and 150 mg/kg, 30 min before the behavioral evaluation in the elevated plus maze (EPM). Both infuse and wax ethanolic fraction at the dosage 150 mg/kg, vo, increased the number and the percentage of open arm entries of rats and mice. The aqueous and butanolic fractions, obtained from ethanolic extract, failed to induce anxiolytic effect. The treatment of mice with flumazenil (Ro 15-1788), 1.5, 2.0 and 2.5 mg/kg, i.p., 15-min before the administration of infuse or wax fraction, 150 mg/kg, vo, blocked the infuse or wax fraction-induced anxiolytic effect. The LD50 for the wax fraction was 1000 mg/kg. In conclusion, the infuse and wax ethanolic fraction of R. brasiliensis present anxiolytic effect in rats and mice. In addition, it is suggested that the anxiolytic effect may be attributed at least to one liposoluble principle with low acute toxicity which may be acting as an agonist on GABA(A)-benzodiazepine receptor complex. (C) 1998 Elsevier B.V. Ireland Ltd. All rights reserved.

Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

We studied the effects of islet of Langerhans transplantation (IT) on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC), group GIT included 15 alloxan-induced diabetic rats (DC), and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT). Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT), mesangial enlargement (ME), and Bowman's capsule thickening (BCT) in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01). However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE) and tubular lumen protein (PRO) observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation.

Transcriptional Profile of Diuron-Induced Toxicity on the Urinary Bladder of Male Wistar Rats to Inform Mode of Action

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

Gastric proliferative lesions induced by duodenogastric reflux in rats

OBJETIVO: Avaliar as lesões proliferativas que se desenvolvem na mucosa gástrica de ratos Wistar após modelo específico de refluxo duodeno-gástrico. MÉTODOS: Foram utilizados 75 ratos adultos machos divididos em três grupos experimentais: o grupo I (controle) submetido a gastrotomia na parede posterior do estômago glandular (25 animais); o grupo II (RDG), foi submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular (25 animais) e o grupo III (RDG-P) submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular, com secção e fechamento da alça (25 animais). Os animais foram observados durante 36 semanas, após o que foram realizados estudos macroscópicos e microscópicos da anastomose gastrojejunal, da região pré-pilórica e região escamosa do estômago. RESULTADOS: Os animais do Grupo I não apresentaram nenhum tipo de lesão. No grupo II observou-se 40% de lesões do tipo hiperplasia adenomatosa na anastomose e 12% de hiperplasia escamosa. No grupo III obteve-se 40% de hiperplasia adenomatosa na mucosa pré-pilórica, 72 % de hiperplasia adenomatosa na mucosa da anastomose, 20% de hiperplasia escamosa e 12 % de adenocarcinoma. CONCLUSÕES: O refluxo duodeno-gástrico induz a alta freqüência de lesões proliferativas na mucosa adjacente à anastomose gastrojejunal ou na mucosa pré-pilórica e o adenocarcinoma é um evento raro neste modelo experimental.

Effect of photodynamic therapy on the healing of cutaneous third-degree-burn: histological study in rats

The aim of this study was to conduct a histological assessment of the effect of photodynamic therapy (PDT) on the repairing of third-degree-burn wounds made on the backs of rats with a heated scalpel. Ninety-six rats were divided into groups: G1, control (n = 24), cold scalpel; G2, burned, heated scalpel (n = 24); G3, low-level laser therapy (LLLT) (n = 24), on burns; and G4, photodynamic therapy (PDT) (n = 24), toluidine-O blue (100 A mu g/ml) and LLLT treatment on burns. The laser (685 nm) was applied in continuous mode, 50 mW, 4.5 J/cm(2), contact mode at nine points (9 s/point). Eight animals in each group were killed at 3 days, 7 days or 14 days after surgery, and tissue specimens containing the whole wounded area were removed and processed for histological analysis; the results were statistically analyzed with Kruskal-Wallis and Dunn's tests (P < 0.05). The results demonstrated significant differences between G2 and G3, and between G2 and G4, at both 3 days and 7 days, with regard to acute inflammation scores; G1 and G2 showed significant differences when compared with G4 at 3 days, with regard to neo-angiogenesis scores; G1 and G2 were statistically different from G3 and G4 at both 3 days and 7 days, with regard to re-epithelization scores; G2 showed statistically significant differences when compared with G3 and G4 with regard to collagen fiber scores at 7 days. LLLT and PDT acted as a biostimulating coadjuvant agent, balancing the undesirable effect of the burn on the wound healing process, acting mainly in the early healing stages, hastening inflammation and increasing collagen deposition.