2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oxidation of melatonin by AAPH-derived peroxyl radicals: Evidence of a pro-oxidant effect of melatonin

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

Effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress

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

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.

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.

Trimetazidine and N-acetylcysteine in attenuating hind-limb ischemia and reperfusion injuries: experimental study in rats

Aim. Lower-limb traumatic injury associated with ischemia and followed by reperfusion (I/R) is a common severe situation in muscle lesions due to trauma and hypoxia followed by local and systemic injuries induced by oxygen-derived free radical release during reperfusion. The aim of this study was to evaluate the attenuating effects of trimetazidine (TMZ) and N-acetylcysteine (NAC) in such situation.Methods. The muscles at the root of the right hind limb of Wistar rats were cross-sectioned, preserving femoral vessels and nerves and clamping the femoral artery for four hours. The clamp was then released and the femoral artery has been reperfused for 2 hours. Rats were randomly divided in groups of ten as follows: Group 1: sham I/R, treated with saline; Group 2: I/R, treated with saline; Group 3: sham I/R, treated with TMZ (7.5 mg/kg/dose); Group 4: sham I/R, treated with NAC (375 mg/kg/dose); Group 5: I/R treated with TMZ (7.5 mg/kg/dose); Group 6: I/R treated with NAC (375 mg/kg/dose). All rats received two intravenous bolus injections of the drugs, one before ischemia and one before reperfusion. Oxidative stress in plasma (MDA, total, oxidized and reduced glutathione), creatinephosphokinase (CPK), optical and electron microscopy and pelvic extremity circumference and volume were studied.Results. No statistical differences were found between the groups for MDA or total and reduced glutathione. Oxidized glutathione increased significantly in groups 5 and 2. Limb circumference as well as limb volume increased in all groups over time, mainly in groups 5, 2 and 1. CPK increased in all groups, being highest in groups 5, 6 and 2. Histological lesions were present in all but sham groups, being less severe in group 6. Soleus muscle analyses at electron microscopy exhibit some degree of alteration in all groups.Conclusion. This experimental model simulated severe limb trauma associated with ischemia and reperfusion, and, as such, it was aggressive, causing severe injury and local inflammatory reaction. The model did not show antioxidant action from NAC, and possible antioxidant action from TMZ was insufficient to attenuate tissue injuries. [Int Angiol 2009;28:412-7]

Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density lipoprotein and antioxidant defenses in rats

To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum antioxidant defenses and markers of oxidative stress, male Wistar rats were divided into two groups (n = 10): (C) receiving intramuscularly a single daily dose of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of 10 mg/kg diclofenac sodium (C14H10C12NNaO2). After 28 days diclofenac-treated rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid hydroperoxide than C. Total antioxidant substances and superoxide dismutase were increased in diclofenac-treated rats, while no significant changes were observed in catalase, glutathione peroxidase and nitric oxide. A perincubation test done to examine the possibility of mechanism-based activation showed that diclofenac had no effect on maximal superoxide dismutase velocity, but significantly reduced the Michaelis-Menten (K-M) constant, indicating that diclofenac induced SOD activation increasing substrate linkage affinity to the enzyme-catalytic site. In conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving antioxidant defense. It appears that the application of this agent may be feasible and beneficial for serum antioxidant protection, which certainly would bring new insights on dyslipidemia control. (C) 2008 Elsevier B.V. All rights reserved.

Alterations in myocardial collagen content affect rat papillary muscle function

We investigated the influence of myocardial collagen volume fraction (CVF, %) and hydroxyproline concentration (mu g/mg) on rat papillary muscle function. Collagen excess was obtained in 10 rats with unilateral renal ischemia for 5 wk followed by 3-wk treatment with ramipril (20 mg . kg(-1) . day(-1)) (RHTR rats; CVF = 3.83 +/- 0.80, hydroxyproline = 3.79 +/- 0.50). Collagen degradation was induced by double infusion of oxidized glutathione (GSSG rats; CVF 5 2.45 +/- 0.52, hydroxyproline = 2.85 +/- 0.18). Nine untreated rats were used as controls (CFV = 3.04 +/- 0.58, hydroxyproline = 3.21 +/- 0.30). Active stiffness (AS; g . cm(-2) . %L-max(-1)) and myocyte cross-sectional area (MA; mu m(2)) were increased in the GSSG rats compared with controls [AS 5.86 vs. 3.96 (P< 0.05); MA 363 +/- 59 vs. 305 +/- 28 (P< 0.05)]. In GSSG and RHTR groups the passive tension-length curves were shifted downwards, indicating decreased passive stiffness, and upwards, indicating increased passive stiffness, respectively. Decreased collagen content induced by GSSG is related to myocyte hypertrophy, decreased passive stiffness, and increased AS, and increased collagen concentration causes myocardial diastolic dysfunction with no effect on systolic function.

Effects of swim training on liver carcinogenesis in male Wistar rats fed a low-fat or high-fat diet

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

Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects

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

THE ROLE of OXIDATIVE STRESS and LIPID PEROXIDATION IN VENTRICULAR REMODELING INDUCED BY TOBACCO SMOKE EXPOSURE AFTER MYOCARDIAL INFARCTION

OBJECTIVE: To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction.METHODS: After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses.RESULTS: Rats in the ETS group showed higher diastolic (C = 1.52 +/- 0.4 mm(2), ETS = 1.95 +/- 0.4 mm(2); p=0.032) and systolic (C = 1.03 +/- 0.3, ETS = 1.36 +/- 0.4 mm(2)/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 +/- 10.1 %, ETS = 19.2 +/- 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 +/- 2.2, ETS = 5.1 +/- 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 +/- 7.6 nmol/mg of protein, ETS = 40.7 +/- 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 +/- 0.1 nmol/g of protein, ETS = 0.9 +/- 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 +/- 0.2 nmol/mg of tissue, ETS = 0.1 +/- 0.1 nmol/mg of tissue; p=0.08).CONCLUSION: In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular re-remodeling after myocardial infarction.

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influências de dietas ricas em ácidos graxos saturados e insaturados sobre o miocárdio de ratos

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

Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions

Bauhinia forficata, commonly known as paw-of-cow, is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4(th) day of pregnancy, 600 mg/kg from 5(th) to 14(th) day and 1000 mg/kg from 15(th) to 20(th) day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, bypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

Effect of Bauhinia forficata aqueous extract on the maternal-fetal outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats

Ethnopharmacological relevance: Bauhinia forficata Link, commonly known as paw-of-cow, is widely used in Brazilian folk medicine for the treatment of diabetes.Aim of this study: To evaluate the effect of Bauhinia forficata treatment on maternal-fetal outcome and antioxidant systems of streptozotocin-induced diabetic rats.Materials and methods: Virgin female Wistar rats were injected with 40 mg/kg streptozotocin before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats at increasing doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. At day 21 of pregnancy the rats were anaesthetized with ether and a maternal blood sample was collected for the determination superoxide dismutase (SOD) and reduced glutathione (GSH). The gravid uterus was weighed with its contents and fetuses were analyzed.Results and conclusion: The data showed that the diabetic dams presented an increased glycemic level, resorption, placental weight, placental index, and fetal anomalies, and reduced GSH and SOD determinations, live fetuses, maternal weight gain, gravid uterine weight, and fetal weight. It was also verified that Bauhinia forficata treatment had no hypoglycemic effect, did not improve maternal outcomes in diabetic rats, but it contributed to maintain GSH concentration similarly to non-diabetic groups, suggesting relation with the decreased incidence of visceral anomalies. (C) 2007 Elsevier B.V. All rights reserved.