RESUMO
BACKGROUND: Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully used as local anesthetic and muscle relaxants to treat a variety of ailments. The primary mechanism of action of these toxins occurs by blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or derivatives. However, most of these non-classical sodium channel blockers act with a reduced time effect as well as ensuing neurotoxicity. NEW METHOD: In this report, we show that the use of local NeoSTX injections inactivates the hippocampal neuronal activity reversibly with a by long-term dynamics, without neuronal damage. RESULTS: A single 10 ng/µl injection of NeoSTX in the dorsal CA1 region abolished for up to 48 h memory capacities and neuronal activity measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals fully recover their memory capacities and hippocampal neuronal activity. The histological inspection of NeoSTX injected brain regions revealed no damage to the tissue or reactive gliosis, similar to vehicle injection. Acute electrophysiological recording in vivo shows, also, minimal spreading of the NeoSTX in the cerebral tissue. COMPARISON WITH EXISTING METHODS: Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage. CONCLUSION: NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses.
Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Saxitoxina/análogos & derivados , Bloqueadores dos Canais de Sódio/administração & dosagem , Memória Espacial/efeitos dos fármacos , Amnésia/induzido quimicamente , Animais , Região CA1 Hipocampal/fisiologia , Masculino , Neurônios/fisiologia , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos , Saxitoxina/administração & dosagemRESUMO
BACKGROUND: Human papillomavirus (HPV) is a highly prevalent sexually transmitted virus causing cytological alterations that precede cervical cancer. Approximately 130 genotypes have been sequenced. Low-grade squamous intraepithelial lesions (LSIL) are the most frequent cytological alteration and have an uncertain behavior. OBJECTIVES: To analyze the frequency of HPV types in LSIL and their association with the regression, persistence or progression of these lesions. METHODS: A cohort study of forty patients with LSIL cytology was conducted from December 2007 to March 2011. The follow-up lasted two years and included cytology and colposcopy. HPV detection was performed using PCR, and genotyping was performed using PCR-specific and RFLP techniques. RESULTS: DNA-HPV was detected in 87% (35/40) of the cases, with oncogenic HPV accounting for 76%; type 16 in 32% (11/35) and type 18 in 20%. LSIL regression, persistence and progression rates at the end of the study were 60%, 23% and 17%, respectively. There was 50% regression in lesions in the high oncogenic risk group (types 16 and 18). CONCLUSION: HPV 16 was the most frequent genotype found in LSIL. The persistence and progression of the LSIL were related to the persistence of oncogenic HPV. The longer the follow-up time, the lower the LSIL persistence rate and the higher its regression rate; the progression rate remained stable. In addition to the presence of oncogenic HPV, other factors are necessary for the progression of LSIL.
Assuntos
Infecções por Papillomavirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Progressão da Doença , Feminino , Genótipo , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.
Assuntos
Anticarcinógenos/farmacologia , Glutationa/metabolismo , Isotiocianatos/farmacologia , Ácido Quinolínico/metabolismo , Animais , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Doenças Neurodegenerativas/metabolismo , Ratos Wistar , SulfóxidosRESUMO
The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1α was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.
Assuntos
Hipocampo/metabolismo , Hipocampo/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/fisiologia , Animais , Western Blotting , Imuno-Histoquímica , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Ratos , Ratos WistarRESUMO
Quinolinic acid (QA)-induced overactivation of N-methyl-d-aspartate receptors yields excitotoxicity, oxidative stress and mitochondrial dysfunction, which altogether contribute to trigger a wide variety of toxic pathways with biochemical, behavioral and neuropathological alterations similar to those observed in Huntington's disease. Noteworthy, in the brains of these patients, increased expression of heme oxygenase-1 (HO-1) levels can be found. It has been proposed that this enzyme can exert a dual role, as it can be either protective or deleterious to the CNS. While some evidence indicates that its overexpression affords cellular anti-oxidant protection due to decreased concentrations of its pro-oxidative substrate heme group, and increased bilirubin levels, other reports established that high HO-1 expression and activity may result in a pro-oxidizing atmosphere due to a release of Fe(2+). In this work, we examined the temporal evolution of oxidative damage to proteins, HO-1 expression, immunoreactivity, total activity, and cell death after 1, 3, 5 and 7 days of an intrastriatal QA infusion (240 nmol/µl). QA was found to induce cellular degeneration, increasing carbonylated proteins and generating a transitory response in HO-1 mRNA, protein content, and immunoreactivity and activity in nerve cells. In order to study the role of HO-1 in the QA-induced cellular death, the tin protoporphyrin IX (SnPP), a well-known HO inhibitor, was administered to rats (30 µmol/kg, i.p.). The administration of SnPP to animals treated with QA inhibited the HO activation, and exacerbated the striatal cell damage induced by QA. Our findings reveal a potential modulatory role of HO-1 in the toxic paradigm evoked by QA in rats. This evidence provides a valuable tool for further approaches on HO-1 regulation in neurotoxic paradigms.
Assuntos
Corpo Estriado/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Degeneração Neural/metabolismo , Estresse Oxidativo/fisiologia , Regulação para Cima/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Heme Oxigenase-1/metabolismo , Masculino , Metaloporfirinas/farmacologia , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Protoporfirinas/farmacologia , Ácido Quinolínico , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 µM) were tested in cerebellum and forebrain homogenates exposed to 5 µM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 µM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 µM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 µM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 µM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.
Assuntos
Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Ácido Cinurênico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Células Cultivadas , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Compostos Ferrosos/antagonistas & inibidores , Compostos Ferrosos/farmacologia , Hidróxidos/metabolismo , Ácido Cinurênico/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microinjeções , Nitrocompostos/antagonistas & inibidores , Nitrocompostos/farmacologia , Oócitos/metabolismo , Propionatos/antagonistas & inibidores , Propionatos/farmacologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Xenopus laevisRESUMO
Brain damage from neonatal hypoxia-ischemia (HI) plays a major role in neonatal mortality and morbidity. Using the Rice-Vannucci model of HI in rats, we verified that 8 days after HI injury, adenosine deaminase (ADA), N-acetyl-glucosaminidase (NAG) and myeloperoxidase (MPO) activities increased in the left hemisphere hippocampus (HI group); however, the activity of 5'-nucleotidase (5'NT) remained unchanged. In the hematoxylin-eosin analysis (HE), we detected selective and delayed degeneration of hippocampal pyramidal neurons and astroglial reaction accompanied by glial fibrillary acidic protein (GFAP)-positive and vimentin-positive in the immunohistochemistry analysis in the HI group compared with the control group. We observed the selective necrosis of neurons, vascular endothelial proliferation and inflammatory response accompanied by the increase of the key enzyme of adenosine metabolism in the HI group. The increase of ADA activity, despite the 5'NT activity was not altered, indicates the predominance of ADA activity in the postischemic homeostasis of extra cellular adenosine. The presence of leukocytes into the ischemic areas displays the possible importance of the neutrophil-macrophages associated with the increase of MPO and NAG activities 8 days after HI. These findings may contribute to the evaluation of some consequences of the damage caused by neonatal HI.
Assuntos
Hipocampo/enzimologia , Hipocampo/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Astrócitos/patologia , Hexosaminidases/metabolismo , Hipocampo/lesões , Hipóxia-Isquemia Encefálica/imunologia , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Peroxidase/metabolismo , Ratos , Ratos WistarRESUMO
Neuronal discharge and local field potential (LFP) oscillations in the olfactory bulb (OB) are modulated by odorant stimulation. The LFP oscillations have been proposed as the mechanism that facilitates synchronization of OB output neurons and the representation of similar odorants. Gamma LFP oscillations depend on the OB inhibitory network and early sensory deprivation modifies this inhibitory network. However, little is known about the LFP oscillations and neuronal discharge in the deprived OB. We examined the mitral/tufted (MT) cells' oscillatory activity and LFP oscillations in both sensory-deprived and normal OBs in urethane anesthetized rats. We found that MT cells in deprived and normal OBs have similar basal mean firing rate; 44% of the recorded cells in deprived OB and only 8% of the cells in normal OB showed firing rate modulation by odorants, both exhibiting a similar ratio of excitatory to inhibitory responses. A fraction of MT cells exhibited oscillatory discharge centered on gamma (60-70 Hz) and beta (20 Hz) frequencies, although this feature was not consistently dependent on odorant stimulation. Odorants decreased the LFP oscillatory power in the gamma band (35-90 Hz) and increased the power in the beta band (12-30 Hz). The modulation of LFP oscillations by odorants was also predominant in the deprived (53%) compared to the normal OB (17%). In contrast, a higher fraction of MT cells' discharge was locked to the gamma LFP cycle in the normal OB. These results suggest that early unilateral olfactory deprivation increases the OB sensitivity to odorants and reduce the temporal synchrony between unitary activity and gamma LFP oscillations without altering the basal neuronal discharge.
Assuntos
Neurônios/fisiologia , Odorantes , Bulbo Olfatório/fisiologia , Privação Sensorial , Potenciais de Ação , Animais , Periodicidade , Ratos , Ratos Sprague-DawleyRESUMO
Cigarette smoke is a complex mixture of various toxic substances that are capable of initiating oxidative damage and promoting blood platelet alterations. In this study, we investigated the activities of the ectoenzymes NTPDase (ectonucleoside triphosphate diphosphohydrolase, CD39) and 5'-nucleotidase (CD73) in platelets as well as adenosine deaminase (ADA) in the plasma of rats exposed to aged and diluted sidestream smoke during 4 weeks. The rats were divided into two groups: I (control) and II (exposed to smoke). After the exposure period, blood was collected and the platelets and plasma were separated for enzymatic assay. The results demonstrated that NTPDase (with ATP as substrate) and 5'-nucleotidase (AMP as substrate) activities were significantly higher in group II (p < 0.05) as compared to group I, while no significant difference was observed for NTPDase with ADP as substrate. The ADA activity was significantly reduced in group II (p < 0.05) as compared with group I. Platelet aggregation was significantly increased in group II (p < 0.05) as compared with group I. We suggest that these alterations in the activity of enzymes from the purinergic system are associated with an increase in platelet aggregation. However, our study has demonstrated that the organism tries to compensate for this enhanced aggregation by increasing hydrolysis of AMP and reducing hydrolysis of adenosine, a potent inhibitor of aggregation and an important modulator of vascular tone.
Assuntos
Adenosina Desaminase/metabolismo , Adenosina Trifosfatases/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , 5'-Nucleotidase/sangue , Adenosina/sangue , Animais , Gasometria , Plaquetas/enzimologia , Carboxihemoglobina/metabolismo , Concentração de Íons de Hidrogênio , Pulmão/enzimologia , Pulmão/patologia , Masculino , Agregação Plaquetária/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Ratos , Ratos Wistar , Nicotiana/químicaRESUMO
Many studies have now demonstrated that neurons in the visual cortex of cats and monkeys change their activity when stimuli are presented beyond their classical receptive field, and that these responses are not readily apparent from their receptive field properties. However few studies have been conducted to investigate the discharge properties of neurons in the visual cortex of animals when they are allow to freely view natural images. We employ tetrodes, which enable simultaneous and separable recordings of small numbers of neighboring neurons, to record 102 single units from 59 sites from areas 17 and 18 of two alert cats. While the animals viewed either natural images or black screens, they made frequent saccadic eye movements and gaze fixations. Fixations onto an image's location increased neuronal firing peaking at 80-100 ms after the fixation onset, to then decrease steadily with time despite continuous fixation. Saccades trigger a fast decrease in firing rate for both images and darkness. When we examined the incidence of correlated firing, we observed significant synchrony during the initial phases of visual fixations when the animals viewed natural scenes. Such synchrony was absent during saccadic eye movements and during eye movements in darkness. Our data revealed that scanning of natural scenes is associated with a rapid succession of distinct fixation-related activation patterns that included transient rate changes and excess coincident firing. The transient nature of these synchronization phenomena suggests a fast acting mechanism, which is in good agreement with the evidence that basic operations of scene analysis must be accomplished within a few tens of milliseconds in primary visual cortex.
Assuntos
Potenciais de Ação/fisiologia , Fixação Ocular/fisiologia , Neurônios/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Gatos , Sincronização Cortical , Masculino , Orientação/fisiologia , Estimulação Luminosa , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Percepção Espacial/fisiologia , Campos Visuais/fisiologiaRESUMO
Olfactory perception initiates in the nasal epithelium wherefrom olfactory receptor neurons--expressing the same receptor protein--project and converge in two different glomeruli within each olfactory bulb. Recent evidence suggests that glomeruli are isolated functional units, arranged in a chemotopic manner in the olfactory bulb. Exposure to odorants leads to the activation of specific populations of glomeruli. In rodents, about 25-50 mitral/tufted cells project their primary dendrites to a single glomerulus receiving similar sensory input. Yet, little is known about the properties of neighboring mitral/tufted cells connected to one or a few neighboring glomeruli. We used tetrodes to simultaneously record multiple single-unit activity in the mitral cell layer of anesthetized, freely breathing rats while exposed to mixtures of chemically related compounds. First, we characterized the odorant-induced modifications in firing rate of neighboring mitral/tufted cells and found that they do not share odorant response profiles. Individual units showed a long silent (11.01 ms) period with no oscillatory activity. Cross-correlation analysis between neighboring mitral/tufted cells revealed negligible synchronous activity among them. Finally, we show that respiratory-related temporal patterns are dissimilar among neighboring mitral/tufted cells and also that odorant stimulation results in an individual modification that is not necessarily shared by neighboring mitral/tufted cells. These results show that neighboring mitral/tufted cells frequently exhibit dissimilar response properties, which are not consistent with a precise chemotopic map at the mitral/tufted cell layer in the olfactory bulb.
Assuntos
Potenciais de Ação/fisiologia , Neurônios/fisiologia , Odorantes , Bulbo Olfatório/citologia , Animais , Relógios Biológicos/fisiologia , Feminino , Masculino , Inibição Neural/fisiologia , Neurônios/classificação , Condutos Olfatórios/fisiologia , Ratos , Ratos Sprague-Dawley , Olfato/fisiologiaRESUMO
During the last decade, there has been a significant increase in the use of computers in biomedical research. In particular, the use of these instruments in experimental control, as well as in the acquisition and storage of experimental data, has become universal. The current capacity of these machines enables the precise manipulation of many experimental variables and allows for very fast acquisition of data. In this article, we discuss the fundamentals of small personal computers and its use in experimental control and data acquisition. Further, we discuss technical aspects related to the management of measurement instrument's control and their technical limitations. Electrical recordings from the cerebral cortex are used as examples to illustrate the different aspect included in this article.
Assuntos
Processamento Eletrônico de Dados , Armazenamento e Recuperação da Informação/métodos , Pesquisa , Animais , Humanos , Microcomputadores , Modelos BiológicosRESUMO
A personal computer equipped with an analog-to-digital conversion card is able to input, store and display signals of biomedical interest. These signals can additionally be submitted to ad-hoc software for analysis and diagnosis. Data acquisition is based on the sampling of a signal at a given rate and amplitude resolution. The automation of signal processing conveys syntactic aspects (data transduction, conditioning and reduction); and semantic aspects (feature extraction to describe and characterize the signal and diagnostic classification). The analytical approach that is at the basis of computer programming allows for the successful resolution of apparently complex tasks. Two basic principles involved are the definition of simple fundamental functions that are then iterated and the modular subdivision of tasks. These two principles are illustrated, respectively, by presenting the algorithm that detects relevant elements for the analysis of a polysomnogram, and the task flow in systems that automate electrocardiographic reports.
Assuntos
Computação em Informática Médica , Algoritmos , Conversão Análogo-Digital , Apresentação de Dados , Diagnóstico por Computador , Eletrocardiografia , Microcomputadores , Processamento de Sinais Assistido por Computador , Design de Software , Interface Usuário-ComputadorRESUMO
Reactive oxygen species are involved in gentamicin (GM) nephrotoxicity, and garlic is effective in preventing or ameliorating oxidative stress. Therefore, the effect of garlic on GM nephrotoxicity was investigated in this work. Four groups of rats were studied: (i) fed normal diet (CT), (ii) treated with GM (GM), (iii) fed 2% garlic diet (GA), and (iv) treated with GM and 2% garlic diet (GM + GA). Rats were placed in metabolic cages and GM nephrotoxicity was induced by injections of GM (75 mg/kg every 12 h) for 6 d. Lipoperoxidation and enzyme determinations were made in renal cortex on day 7. GM nephrotoxicity was made evident on day 7 by (i) tubular histological damage, (ii) enhanced BUN and urinary excretion of N-acetyl-beta-D-glucosaminidase, and (iii) decreased creatinine clearance. These alterations were prevented or ameliorated in GM + GA group. The rise in lipoperoxidation and the decrease in Mn-SOD and glutathione peroxidase (GPx) activities observed in the GM group, were prevented in the GM + GA group. Cu, Zn-SOD activity and Mn-SOD and Cu,Zn-SOD content did not change. CAT activity and content decreased in the GM, GA, and GM + GA groups. CAT mRNA levels decreased in the GM group. The protective effect of garlic is associated with the prevention of the decrease of Mn-SOD and GPx activities and with the rise of lipoperoxidation in renal cortex.
Assuntos
Catalase/metabolismo , Alho , Gentamicinas/toxicidade , Glutationa Peroxidase/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Peroxidação de Lipídeos/efeitos dos fármacos , Plantas Medicinais , Superóxido Dismutase/genética , Acetilglucosaminidase/urina , Animais , Nitrogênio da Ureia Sanguínea , Catalase/genética , Dieta , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Rim/patologia , Córtex Renal/efeitos dos fármacos , Córtex Renal/patologia , Masculino , Estresse Oxidativo , Proteinúria , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismoRESUMO
The response of endogenous antioxidants to the N-methyl-D-aspartate (NMDA) receptor agonist and excitotoxin, quinolinic acid (QUIN), was investigated in rat corpus striatum. Animals treated with QUIN (240 nmol/microl), were sacrificed at 120 min after a single intrastriatal injection to examine the alterations in the levels of both reduced (GSH) and oxidized (GSSG) glutathione, and the activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (Gpx). Changes in the rate of lipid peroxidation (LP) were also measured after exposure to different doses of QUIN (60, 120, 240 and 480 nmol/microl) as an index of oxidative stress. When compared to control, lipid peroxidation was increased at QUIN doses of 240 and 480 nmol/microl. Striatal levels of GSH and GSSG were decreased and increased, respectively, after QUIN injection; whereas GPx activity was unchanged. Cytosolic copper/zinc SOD (CuZn-SOD) activity decreased after treatment, while mitochondrial manganese SOD (Mn-SOD) was unchanged. The alterations observed on these antioxidant systems suggest that QUIN toxicity is mediated by specific mechanisms leading to oxidative stress.