LACK of SEX and ESTROUS-CYCLE EFFECTS ON the ACTIVITY of 3 ANTIOXIDANT ENZYMES in RATS

The activity of antioxidant enzymes was investigated in red blood cells of male and female Wistar rats 3-4 months of age. Superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), and glutathione peroxidase (EC 1.11.1.9) did not show any significant variation in the different phases of the estrous cycle. No differences were observed for the three enzymes related to the sex of young rats. the present data enable us to consider that sexual differences as well as the changes in estrous cycle do not interfere in erythrocyte antioxidant enzymatic defense of rats.ESCOLA PAULISTA MED,DEPT BIOCHEM,BR-04023062 São Paulo,BRAZILESCOLA PAULISTA MED,DEPT PSYCHOBIOL,BR-04023062 São Paulo,BRAZILESCOLA PAULISTA MED,DEPT BIOCHEM,BR-04023062 São Paulo,BRAZILESCOLA PAULISTA MED,DEPT PSYCHOBIOL,BR-04023062 São Paulo,BRAZILWeb of Scienc

ESTERASE-D ASSAY in BRAZILIAN RETINOBLASTOMA FAMILIES

ESCOLA PAULISTA MED SCH,DEPT MORPHOL,BIOCHEM GENET LAB,BR-04023 São Paulo,SP,BRAZILHOSP AC CARMARGO FUNDACAO ANTONIO PRUDENTE,DEPT OPHTHALMOL,São Paulo,SP,BRAZILESCOLA PAULISTA MED SCH,DEPT MORPHOL,BIOCHEM GENET LAB,BR-04023 São Paulo,SP,BRAZILWeb of Scienc

Antioxidant defense in rat brain after chronic treatment with anorectic drugs

Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5H-isoindole) although not chemically related to the phenylethylamine group, shows a pharmacological profile similar to that of amphetamines. in rats these anorectic drugs enhance dopamine (DA) turnover, which is the mechanism that causes anorexia. It has been hypothesized that amphetamine causes a long-lasting depletion of DA, a decrease of dopaminergic transport pumps and nerve terminal degeneration increasing. These actions provide a cellular environment encouraging the autoxidation of DA that may lead to lipid peroxidation and neuronal damage. Considering that both drugs may cause neuronal damage by oxidative mechanisms, this study was conducted to investigate the action of mazindol and methamphetamine on brain cell antioxidant defense system and to investigate whether animal age is important in the antioxidant response to chronic anorectic administration. the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the total glutathione (GSH) content in brains of rats, were measured. the animals (2 groups with 5 and 18 months old) were treated for 5 months (i.p.) with mazindol (10 mg/kg body weight/day), methamphetamine (2.5 mg/kg body weight/day) or saline. the results obtained showed no differences between SOD, CAT, GPx activities and GSH content in the brain of animals treated with saline compared with both drugs, either in 10-month or 23-month groups. On the other hand, brain total GSH content of old animals was found to be lower than that from young ones, independent of the treatment. SOD activity was found to be increased, CAT unchanged and GPx decreased, in the brain of old animals, treated with both drugs or saline. These findings led us to conclude that the chronic administration of mazindol and methamphetamine have no effects on the antioxidant systems studied either in young (10 months) or in old (23 months) rats.Universidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PSYCHOBIOL,São Paulo,BRAZILUniversidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT PSYCHOBIOL,São Paulo,BRAZILWeb of Scienc

Efficacy of Novel Carbon Nanoparticle Antioxidant Therapy in a Severe Model of Reversible Middle Cerebral Artery Stroke in Acutely Hyperglycemic Rats

IntroductionWhile oxidative stress can be measured during transient cerebral ischemia, antioxidant therapies for ischemic stroke have been clinically unsuccessful. Many antioxidants are limited in their range and/or capacity for quenching radicals and can generate toxic intermediates overwhelming depleted endogenous protection. We developed a new antioxidant class, 40 nm × 2 nm carbon nanoparticles, hydrophilic carbon clusters, conjugated to poly(ethylene glycol) termed PEG-HCCs. These particles are high-capacity superoxide dismutase mimics, are effective against hydroxyl radical, and restore the balance between nitric oxide and superoxide in the vasculature. Here, we report the effects of PEG-HCCs administered during reperfusion after transient middle cerebral artery occlusion (tMCAO) by suture in the rat under hyperglycemic conditions. Hyperglycemia occurs in one-third of stroke patients and worsens clinical outcome. In animal models, this worsening occurs largely by accelerating elaboration of reactive oxygen species (ROS) during reperfusion.MethodsPEG-HCCs were studied for their protective ability against hydrogen peroxide in b.End3 brain endothelial cell line and E17 primary cortical neuron cultures. In vivo, hyperglycemia was induced by streptozotocin injection 2 days before tMCAO. 58 Male Sprague-Dawley rats were analyzed. They were injected IV with PBS or PEG-HCCs (4 mg/kg 2×) at the time of recanalization after either 90- or 120-min occlusion. Rats were survived for up to 3 days, and infarct volume characteristics and neurological functional outcome (modified Bederson Score) were assessed.ResultsPEG-HCCs were protective against hydrogen peroxide in both culture models. In vivo improvement was found after PEG-HCCs with 90-min ischemia with reduction in infarct size (42%), hemisphere swelling (46%), hemorrhage score (53%), and improvement in Bederson score (70%) (p = 0.068–0.001). Early high mortality in the 2-h in the PBS control group precluded detailed analysis, but a trend was found in improvement in all factors, e.g., reduction in infarct volume (48%; p = 0.034) and a 56% improvement in Bederson score (p = 0.055) with PEG-HCCs.ConclusionThis nano-antioxidant showed some improvement in several outcome measures in a severe model of tMCAO when administered at a clinically relevant time point. Long-term studies and additional models are required to assess potential for clinical use, especially for patients hyperglycemic at the time of their stroke, as these patients have the worst outcomes