RESUMO
Red cabbage (Brassica oleracea L. var. capitata f. rubra DC.) extract has been demonstrated hypolipidemic and antioxidant capacity. Herein, we investigated the effect of red cabbage aqueous extract (RC) or fenofibrate (FF) in oxidative stress induced by Triton WR-1339 in rats. The antioxidant capacity was evaluated through the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and, thiobarbituric reactive species (TBARS) and protein carbonyl (PC) levels in erythrocytes, liver, kidneys, cerebral cortex and hippocampus of male rats. The alterations promoted by Triton WR-1339 in enzymatic antioxidant defense in the liver, kidneys and hippocampus were reversed by RC or FF treatments. The TBARS and PC levels increased in the liver, cerebral cortex and hippocampus of hyperlipidemic rats were decreased by the treatments with RC or FF. These findings demonstrated that RC is a potential therapy to treat diseases not only involving dyslipidemic condition but also oxidative stress.
Assuntos
Antioxidantes/farmacologia , Brassica/química , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Catalase/efeitos dos fármacos , Glutationa Peroxidase/efeitos dos fármacos , Masculino , Oxirredução , Ratos , Ratos Wistar , Superóxido Dismutase , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.
Assuntos
Antimaníacos/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Antimaníacos/uso terapêutico , Antioxidantes/uso terapêutico , Transtorno Bipolar/induzido quimicamente , Estimulantes do Sistema Nervoso Central , Peroxidação de Lipídeos/efeitos dos fármacos , Dimesilato de Lisdexanfetamina , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sinvastatina/uso terapêuticoRESUMO
The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest...
Assuntos
Anfetamina , Estresse Oxidativo , SinvastatinaRESUMO
The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.
Assuntos
Encefalopatias Metabólicas/terapia , Terapia por Exercício/métodos , Ácido Glutâmico/metabolismo , Hiper-Homocisteinemia/terapia , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Animais Recém-Nascidos , Encefalopatias Metabólicas/fisiopatologia , Modelos Animais de Doenças , Hiper-Homocisteinemia/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
In the present study, we investigated the effect of the acute administration of homocysteine (Hcy) on parameters of the coagulation system, as well as fibrinogen and nitrite levels in the blood of rats. In addition, we evaluated the effect of acute hyperhomocysteinemia on thiobarbituric acid-reactive substances in plasma and on antioxidant enzymes activities (superoxide dismutase, catalase, and gluthatione peroxidase) in the erythrocytes of rats. Wistar rats, aged 29 days, received a single subcutaneous dorsal injection of saline (control) or Hcy (0.6 µmol/g body weight). Fifteen minutes, 1 h, 6 h or 12 h after the injection, the rats were euthanized and the blood, plasma, and erythrocytes were collected. Results showed that Hcy significantly increased platelet count in the blood and plasma fibrinogen levels of rats at 15 min and 1 h, but not at 6 h and 12 h, when compared with the control group. Prothrombin time, activated partial thromboplastin time, and nitrite levels significantly decreased in plasma at 15 min and 1 h, but not at 6 h and 12 h after Hcy administration. In addition, hyperhomocysteinemia increased thiobarbituric acid-reactive, an index of lipid peroxidation, in plasma at 15 min and 1 h; decreased the superoxide dismutase and gluthatione peroxidase activity, and increased the catalase activity at 15 min in erythrocytes of rats, suggesting that acute Hcy administration may alter the oxidative status in the blood of rats. Our findings suggest that hypercoagulability and oxidative stress can occur after acute hyperhomocysteinemia, possibly in association, at least in part, with the vascular dysfunction and thromboembolic complications observed in homocystinuric patients.
Assuntos
Coagulação Sanguínea , Hiper-Homocisteinemia/sangue , Estresse Oxidativo , Animais , Catalase/sangue , Eritrócitos/enzimologia , Fibrinogênio/metabolismo , Glutationa Peroxidase/sangue , Nitritos/sangue , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Tempo de Protrombina , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The purpose of this study was to develop a chronic chemically induced model of mild hyperhomocysteinemia in adult rats. We produced levels of Hcy in the blood (30µM), comparable to those considered a risk factor for the development of neurological and cardiovascular diseases, by injecting homocysteine subcutaneously (0.03µmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Using this model, we evaluated the effect of chronic administration of homocysteine on redox status in the blood and cerebral cortex of adult rats. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in the plasma and cerebral cortex, while nitrite levels were reduced in the cerebral cortex, but not in the plasma, of rats subjected to chronic mild hyperhomocysteinemia. Homocysteine was also seen to disrupt enzymatic and non-enzymatic antioxidant defenses in the blood and cerebral cortex of rats. Since experimental animal models are useful for understanding the pathophysiology of human diseases, the present model of mild hyperhomocysteinemia may be useful for the investigation of additional mechanisms involved in tissue alterations caused by homocysteine.
Assuntos
Modelos Animais de Doenças , Homocisteína/administração & dosagem , Homocisteína/farmacologia , Hiper-Homocisteinemia/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Glutationa Peroxidase/metabolismo , Homocisteína/sangue , Humanos , Nitritos/metabolismo , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Depressive disorders, including major depression, are serious and disabling, whose mechanisms are not clearly understood. Since life stressors contribute in some fashion to depression, chronic variable stress (CVS) has been used as an animal model of depression. In the present study we evaluated some parameters of oxidative stress [thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], and inflammatory markers (interleukin 6, C reactive protein, tumor necrosis factor-alpha and nitrites), as well as the activity of butyrylcholinesterase in blood of rats subjected to chronic stress. Homocysteine and folate levels also were measured. Stressed animals were submitted to different mild stressors for 40 days. After CVS, a reduction in weight gain was observed in the stressed group, as well as an increase in immobility time in the forced swimming test as compared with controls. Stressed animals presented a significant increase on TBARS and SOD/CAT ratio, but stress did not alter GPx activity and any inflammatory parameters studied. CVS caused a significant inhibition on serum butyrylcholinesterase activity. Stressed rats had higher plasmatic levels of homocysteine without differences in folate levels. Although it is difficult to extrapolate our findings to the human condition, the alterations observed in this work may be useful to help to understand, at least in part, the pathophysiology of depressive disorders.
Assuntos
Butirilcolinesterase/metabolismo , Depressão/metabolismo , Estresse Oxidativo/fisiologia , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Animais , Proteína C-Reativa/metabolismo , Catalase/sangue , Glutationa Peroxidase/sangue , Imunoensaio , Interleucina-6/sangue , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
In the present study we investigated the effect of acute hyperprolinemia on some parameters of energy metabolism, including the activities of succinate dehydrogenase and cytocrome c oxidase and (14)CO(2) production from glucose and acetate in cerebral cortex of young rats. Lipid peroxidation determined by the levels of thiobarbituric acid-reactive substances, as well as the influence of the antioxidants alpha-tocopherol plus ascorbic acid on the effects elicited by Pro on enzyme activities and on the lipid peroxidation were also evaluated. Wistar rats of 12 and 29 days of life received one subcutaneous injection of saline or proline (12.8 or 18.2 micromol/g body weight, respectively) and were sacrificed 1 h later. In another set of experiments, 5- and 22-day-old rats were pretreated for a week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) plus ascorbic acid (100 mg/kg) or saline. Twelve hours after the last injection, rats received one injection of proline or saline and were sacrificed 1 h later. Results showed that acute administration of proline significantly reduced cytochrome c oxidase activity and increased succinate dehydrogenase activity and (14)CO(2) production in cerebral cortex, suggesting that Pro might disrupt energy metabolism in brain of young rats. In addition, proline administration increased the thiobarbituric acid-reactive substances levels, which were prevented by antioxidants. These findings suggest that mitochondrial dysfunction and oxidative stress may be important contributors to the neurological dysfunction observed in some hyperprolinemic patients and that treatment with antioxidants may be beneficial in this pathology.