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Biomedical subjects

Diogo Onofre Souza

Publications and source records attributed to Diogo Onofre Souza.

At least 19 recordsLinked to original sources
PubMed2006

Effects of maternal protein malnutrition on oxidative markers in the young rat cortex and cerebellum.

Malnutrition affects a large number of children worldwide. Inadequate nutrition during pre- and postnatal period may alter brain development resulting in biochemical, physiological and anatomical changes which in turn could cause behavioral abnormalities. The impairment of the central nervous system following protein deficit have been extensively studied and this deprivation produces deleterious effects upon cerebral structures. The aim of this study was to identify oxidative parameters present in the developing brain as consequence of maternal protein malnutrition. Female Wistar rats were fed a normal protein diet (25% casein) or low protein diet (8% casein) from the time of conception up to 21 days after the parturition. In addition, the diets were supplemented or not with l-methionine. Cortex and cerebellum were removed from offspring to determine the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and the levels of lipoperoxidation (TBARS). Our findings demonstrated heterogeneity in response to protein restriction. The levels of lipoperoxidation were increased in the cerebellum of malnourished offspring. Methionine supplementation caused an increase in lipoperoxidation in both brain structures. CAT activity was decreased in the cerebellum of the offspring supplemented with methionine whereas the cerebellum of malnourished pups with or not methionine supplementation showed a decrease in SOD activity. The activity of SOD in the cortex did not differ among groups. CAT activity, however, was increased in the cortex of malnourished pups supplemented or not with methionine. Thus, these results provide clues to the knowledge of malnutrition effects upon the brain.

Animals↗
PubMed2006

S100B and NSE serum levels in obstructive sleep apnea syndrome.

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a chronic disease ranging from innocuous to life-threatening and causes brain alterations manifested by neuropsychiatric symptoms. Neuron-specific enolase (NSE) and the astrocytic protein S100B are established sensitive peripheral biochemical markers of brain injury. In the present work we measured the serum levels of S100B and NSE in order to evaluate the deleterious effects of OSAS to the brain. PATIENTS AND METHODS: We studied 29 male patients with OSAS and 17 male asymptomatic control subjects with an apnea-hypopnea index (AHI) less than five events per hour. Patients and control subjects were evaluated by full-night polysomnography (PSG) and by Mini International Neuropsychiatric Interview (MINI) for the presence of neuropsychiatric symptoms. In the morning following the PSG, blood was collected and serum levels of S100B and NSE were measured using standard techniques. RESULTS: The AHI in the OSAS group was (mean+/-SD) 27+/-25 AH/h, ranging from 5 to 99 AH/h. S100B was higher in OSAS (0.15+/-0.09 microg/l) than in the control group (0.08+/-0.06 microg/l; P<0.01). Serum NSE was similar in both groups (17.5+/-12.2 vs. 15.8+/-6.8ng/ml). CONCLUSIONS: We report elevated serum S100B levels in OSAS patients in this study.

Adult↗
PubMed2005

Amnesic effect of GMP depends on its conversion to guanosine.

Extracellular guanine-based purines, namely the nucleotides GTP, GDP, GMP and the nucleoside guanosine, exert important neuroprotective and neuromodulator roles in the central nervous system, which may be related to inhibition of the glutamatergic neurotransmission activity. In this study, we investigated GMP effects on mice inhibitory avoidance performance and the dependence on its conversion to guanosine for such effect, by using the ecto-5'-nucleotidase specific inhibitor AOPCP. We also investigated if this conversion occurs in the central nervous system or peripherally, and if guanosine and GMP affect nociception by the tail-flick test. I.p. GMP or guanosine (7.5 mg/kg) or i.c.v. GMP (480 nmol) pretraining administration was amnesic for the inhibitory avoidance task. I.c.v. AOPCP (1 nmol) administration completely reversed the amnesic effect of i.c.v. GMP, but not of i.p. GMP, indicating that peripheral conversion of GMP to guanosine is probably relevant to this effect. AOPCP alone did not interfere with the performance. Furthermore, tail-flick measurement was unaffected by i.p. GMP and guanosine, suggesting that the amnesic effect of both purines was not due to some antinociceptive effect against the footshock used in the task. All these data together, in accordance to those previously observed in studies involving glutamate uptake and seizures reinforce the idea that guanosine is the specific extracellular guanine-based purines effector and indicate that its conversion occurs not only in the central nervous system but also peripherally.

Amnesia↗
PubMed2005

Effect of protein malnutrition on redox state of the hippocampus of rat.

The protein malnutrition is a worldwide problem, affecting mainly newborns and children of developing countries. This deficiency reaches the brain in the most critical period of the development. Various consequences are related to this insult, such as memory disturbance, learning, and behavioral impairment. Protein content of the diet plays an important role on antioxidant mechanisms. This study observed the effects of protein malnutrition on rat hippocampus redox state. Wistar rats were separate in four groups, receiving different diets: first group with 25% casein, protein deficient group with 8% casein, and the same two groups supplemented with methionine (0.15%). Diets were isocaloric and were administered since the prenatal period up to the sacrifice. Rats were decapitated at 21 or 75 days old and hippocampus were isolated for measuring the lipoperoxidation by TBARS method, protein oxidative damage by carbonyl (DNPH) levels, and the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). There was significant alterations in the activities of the enzyme SOD, lipoperoxidation, and protein oxidation in hippocampus of 21 and 75 day-old rats fed with 25% of protein with methionine and the groups fed with low levels of protein (8%) both supplemented or not with methionine. Our data suggest that both the content of protein in the diet and the essential amino acid methionine may alter the antioxidant system and the redox state of the brain.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Propionic and methylmalonic acids increase cAMP levels in slices of cerebral cortex of young rats via adrenergic and glutamatergic mechanisms.

We have previously described that propionic (PA) and methylmalonic (MMA) acids increased the in vitro phosphorylation of cytoskeletal proteins through cAMP-dependent protein kinase and glutamate. In the present study we investigated the in vitro effects of 1 mM glutamate, 2.5 mM MMA and 2.5 mM PA on cAMP levels in the slices of cerebral cortex of young rats. Results showed that PA, MMA and glutamate increased cAMP levels after 30 min of incubation, while the beta-adrenergic agonist epinephrine elicited a similar effect only at a shorter incubation time. Then effects were prevented by the beta-adrenergic antagonist propranolol, rather than by glutamate antagonists (AP5, CNQX and MCPG), suggesting that they were mediated by beta-adrenergic receptors. In addition, glutamate antagonists per se induced increased cAMP levels; however propranolol prevented only the effect elicited by the metabotropic glutamate antagonist MCPG. Taken together, it is feasible that PA and MMA increase cAMP synthesis via a beta-adrenergic/G protein coupled pathway, in a glutamate-dependent manner. Although additional studies will be necessary to evaluate the importance of these observations for the neuropathology of propionic and methylmalonic acidemias, it is possible that high brain cAMP levels may contribute to a certain extent to the neurological dysfunction of the affected individuals.

Adrenergic beta-Agonists↗
PubMed2005

Guanosine enhances glutamate transport capacity in brain cortical slices.

1. The effect of guanosine on L-[3H] glutamate uptake was investigated in brain cortical slices within physio-pathological range of glutamate(1-1000 microM). In these conditions, glutamate uptake was significantly enhanced in slices treated with 100 microM guanosine only at 100 and 300 microM glutamate (44 and 52%, respectively). 2. Evaluation of kinetic parameters showed that guanosine affected significantly only uptake Vmax (23%). 3. The guanosine withdrawal did not abolish its significant effect on glutamate uptake when 100 or 300 microM glutamate were used (an increase of 66 and 35%, respectively). 4. These results support the hypothesis of a protective role for guanosine during excitotoxic conditions when glutamate levels are enhanced (e.g. brain ischemia and seizures), possibly by activating glutamate uptake. Moreover, our results may contribute to understand the antiexcitotoxic mechanism of guanosine on glutamate transport, giving new information concerning its mechanism of action.

Animals↗
PubMed2005

Increase of adenine nucleotide hydrolysis in rat hippocampal slices after seizures induced by quinolinic acid.

Quinolinic acid (QUIN), an endogenous convulsant compound, overstimulates the glutamatergic system stimulating N-methyl-D-aspartate receptors, enhancing glutamate release and inhibiting glutamate uptake. Glutamate releases the neuroprotector adenosine, which in turn reduces glutamate release and depresses the neuronal activity. Additionally, adenine nucleotides are an important source of adenosine, by action of ecto-nucleotidases. Here we evaluated the adenine nucleotide hydrolysis in hippocampal slices of adult rats in different times after seizures induced by QUIN. After 45 min, there was an increase of ATP and ADP hydrolysis. After 5 h, there was an increase of ATP, ADP and AMP hydrolysis. After 12 h, there was an increase only of ATP hydrolysis. After 24 h, all hydrolysis returned to control levels. As slice preparations maintain tissue integrity, this study indicates, more than previously observed with synaptosomal preparations, that the extracellular production of the neuroprotector adenosine may be involved in brain responses to seizures.

Adenine Nucleotides↗
PubMed2004

Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine.

Quinolinic acid (QA) has been used as a model for experimental overstimulation of the glutamatergic system. Glutamate uptake is the main mechanism involved in the maintenance of extracellular glutamate below toxic levels. Guanosine systemically administered prevents quinolinic acid-induced seizures in adult mice and increases basal glutamate uptake by cortical astrocyte culture and slices from young rats. The immature brain differs from the adult brain in its susceptibility to seizures, seizure characteristics, and responses to antiepileptic drugs (AED). Here we investigated the effect of guanosine p.o. on QA-induced seizures in young rats (P12-14) and upon ex vivo glutamate uptake by cortical slices from these animals. I.c.v. infusion of 250 nmol QA induced seizures in all animals and decreased glutamate uptake. I.p. injection of MK-801 and phenobarbital 30 min before QA administration prevented seizures in all animals. Guanosine (7.5 mg/kg) 75 min before QA prevented seizures in 50% of animals as well as prevented the decrease of glutamate uptake in the protected animals. To investigate if the anticonvulsive effect of guanosine was specific for QA-induced seizures, the picrotoxin-induced seizures model was also performed. Pretreatment with phenobarbital i.p. (60 mg/kg-30 min) prevented picrotoxin-induced seizures in all animals, whereas guanosine p.o. (7.5 mg/kg-75 min) and MK-801 i.p. (0.5 mg/kg-30 min) had no effect. Thus, guanosine protection on the QA-induced seizures in young rats and on the decrease of glutamate uptake showed some specificity degree towards the QA-induced toxicity. This points that guanosine could be considered for treatments of epilepsy, and possibly other neurological disorders in children.

Administration, Oral↗
PubMed2004

RC-3095, a bombesin/gastrin-releasing peptide receptor antagonist, impairs aversive but not recognition memory in rats.

Bombesin and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. Bombesin-like peptides also display neuroendocrine activities and regulate neural function. In the present study, we evaluated the effects of the bombesin/GRP receptor antagonist (D-Tpi(6), Leu(13) psi[CH(2)NH]-Leu(14)) bombesin-(6-14) (RC-3095), experimental antitumor drug, on memory in rats. Adult female Wistar rats were treated with an intraperitoneal injection of RC-3095 (0.2, 1.0 or 5.0 mg/kg) 30 min before training in either inhibitory avoidance or novel object recognition tasks. Retention test trials were carried out 1.5 (short-term memory) or 24 h (long-term memory) after training. RC-3095 at the doses of 0.2 or 1.0 mg/kg, but not at the dose of 5.0 mg/kg, impaired both short- and long-term inhibitory avoidance retention, but did not affect recognition memory. The memory-impairing effect of RC-3095 could not be attributed to alterations in sensorimotor functions. The results show that the antitumor drug/GRP antagonist RC-3095 impairs formation of aversive memory.

Animals↗
PubMed2004

Oral administration of guanosine impairs inhibitory avoidance performance in rats and mice.

Extracellular guanine-based purines, mainly the nucleoside guanosine, have recently been shown to exert neuroprotective effects, which seem to be related to antagonism of the glutamatergic system. In this study, we investigated the effects of acute oral administration of guanosine on inhibitory avoidance task in rats and mice. We also studied its effects on locomotor activity, anxiety-related behaviors and mechanisms of action involving the purinergic system. Guanosine (2.0 and 7.5mg/kg, per os), administered 75min pretraining, dose-dependently impaired retention of the inhibitory avoidance task in rats and mice, an effect not prevented by the adenosine receptor antagonist caffeine. Guanosine presented no effects on locomotor activity and anxiety-related behaviors. This amnesic effect of guanosine may be compatible with inhibition of glutamatergic system and seems to be not mediated by adenosine.

Administration, Oral↗
PubMed2004

Riluzole enhances glutamate uptake in rat astrocyte cultures.

1. Riluzole is used for the treatment of amyotrophic lateral sclerosis and reported to have neuroprotective effects in animal models of Parkinson's disease, Huntington's disease, and brain ischemia. The neuroprotective action of riluzole has been attributed to its ability to inhibit glutamate release (A. Doble, Neurology 47(4):233S-241S, 1996). 2. The effect of riluzole on L-[2,3-3H] glutamate uptake was investigated in rat cortical astrocyte cultures. 3. Riluzole showed a biphasic concentration-dependent effect on basal glutamate uptake. At low concentrations (1 and 10 microM) riluzole significantly increased glutamate uptake, whereas from 100 microM promoted a slight reduction. 4. Considering the large range of glutamate levels in the synaptic cleft, we studied the 1 microM riluzole effect on uptake of glutamate at different concentrations (1-1000 microM). Riluzole was more effective at low glutamate concentrations (10 microM), enhancing the basal glutamate uptake up to 42%. 5. The action of riluzole on astrocytic glutamate uptake could be an additional mechanism to its neuroprotective role, perhaps suggesting a modulatory action on glutamatergic system involving glutamate clearance from synaptic cleft.

Animals↗
PubMed2004

Purine nucleoside phosphorylase activity in rat cerebrospinal fluid.

The sequential hydrolysis of purines is present in rat CSF and generates nucleosides as inosine and guanosine that are usual substrates for purine nucleoside phosphorylase (PNP). PNP catalyzes phosphorolysis of the purine nucleosides and deoxynucleosides releasing purine bases. Here we investigated the presence of PNP in CSF of rats using: i) a specific chromophoric analogue of nucleosides, 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG), and ii) an inhibitor of PNP activity, immucillin-H. Additionally, we performed a preliminary kinetic characterization (K(M): Henry-Michaelis-Menten constant; V: maximal velocity) for MESG and inorganic phosphate (Pi). The values of K(M) and V for MESG (n = 3, mean+/-SD) were 142.5+/-29.5 microM and 0.0102+/-0.0006 U mg(-1), respectively. For Pi (n=3, mean+/-SD), the K(M) values and V were 186.8+/-43.7 microM and 0.0104+/-0.0016 U mg(-1), respectively. The results indicated that PNP is present in rat CSF and provided a preliminary kinetic characterization.

Animals↗
PubMed2003

Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice.

Acute administration of intraperitoneal and oral guanosine has been shown to prevent quinolinic acid and alpha-dendrotoxin-induced seizures in rats and mice. In this study, we investigated the effects of 2 weeks ad libitum consumption of guanosine (0.5 mg/ml) added to mice water supply on seizures and lethality induced by the alpha-dendrotoxin, hole-board behavior, inhibitory avoidance task, locomotor activity, motor coordination, rectal temperature, body weight, and water and food consumption. Guanosine prevented seizures in 40% and death in 50% on mice treated with i.c.v. alpha-dendrotoxin; it also impaired inhibitory avoidance memory and increased head-dipping behavior and locomotor activity on the hole-board test. Guanosine consumption did not alter any of the other parameters evaluated. The anticonvulsant, amnesic, and anxyolytic-like effects may be associated with the ability of guanosine in modulating the glutamatergic excitatory system. Adding to previously reported data, these findings suggest a potential role for chronic guanosine in the management of diseases associated with glutamatergic excitotoxicity, including epilepsy and anxiety.

Animals↗
PubMed2003

Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake.

Guanosine (GUO) has been shown to stimulate glutamate uptake in primary astrocyte cultures. The purpose of this study was to determine the effect and specificity of guanine- or adenine-based purines on glutamate and GABA uptake in cultured astrocytes. Stimulatory effect on glutamate uptake was observed with GUO, GMP or GTP. Simultaneous exposure with these guanine-based purines did not show an additive effect. We also investigated a possible interconversion of guanine-based purines during incubation time. Action by GTP was excluded since the hydrolysis resistant GTP analog, GMP-PNP did not stimulate glutamate uptake. Addition of an ecto-5'-nucleotidase inhibitor abolished GMP-stimulatory effect on glutamate uptake, without affecting GUO action. Taken together, these results suggest that GUO is the guanine-based purines responsible for glutamate uptake activation. In addition, the stimulatory effect on glutamate uptake was not observed with adenine-based purines. Moreover, GABA uptake was not activated by GUO. These results point to specificity in the interaction between GUO and the astrocyte glutamate uptake system.

Adenosine Diphosphate↗
PubMed2003

Intrahippocampal infusion of the bombesin/gastrin-releasing peptide antagonist RC-3095 impairs inhibitory avoidance retention.

Bombesin (BN)-like peptides regulate cell proliferation and cancer growth as well as neuroendocrine and neural functions. We evaluated the effects of the BN/gastrin-releasing peptide (GRP) antagonist RC-3095 on memory formation. Male Wistar rats were given a bilateral infusion of saline or RC-3095 (0.2, 1.0 or 5.0 microg) into the dorsal hippocampus either immediately or 2 h after training in an inhibitory avoidance (IA) task. Retention test trials were carried out 1.5 h (short-term memory) and 24 h (long-term memory) after training. RC-3095 impaired both short- and long-term retention only when given immediately after training. The results suggest that the hippocampal BN/GRP receptor system modulates IA memory formation.

Animals↗
PubMed2003

Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors.

Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a noncompetitive NMDA antagonist. The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. Jumping, a major behavioral expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK-801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine-dependent animals treated with IBO or MK-801. This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.

Animals↗
PubMed2003

In vitro effects of selenite and mercuric chloride on liver thiobarbituric acid-reactive substances and non-protein thiols from rats: influences of dietary cholesterol and polyunsaturated and saturated fatty acids.

OBJECTIVE: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. METHODS: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h. RESULTS: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. CONCLUSION: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.

Animals↗