RESUMO
Exercise training has been used for treatment/prevention of many cardiovascular diseases, but the mechanisms need to be clarified. Thus, our aim was to compare oxidative stress parameters between rats submitted to a swimming training and sedentary rats (control). Twelve male rats were divided into two groups: control and exercise training. The exercise training had daily 1 h swimming sessions for 8 weeks and a load (5% of its body mass) was placed in rat's tail. Thereafter the animals were killed, aorta and heart were surgically removed and blood was collected. Body mass gain, thiobarbituric acid reactive species (TBARS), carbonyl content, total reactive antioxidant potential (TRAP), total antioxidant reactivity (TAR), superoxide dismutase (SOD) activity and catalase (CAT) activity were evaluated. The trained rats showed a lower body mass gain and no modifications on heart. An increased SOD activity was observed on aorta after the training, but no changes were seen for CAT activity, which led to an increased SOD/CAT ratio. The arterial TBARS was also increased for trained rats. The decrease in TRAP in exercise training was the single modification on plasma. Our findings suggest that the increased SOD activity could play a role in vascular adaptations to exercise training.
Assuntos
Aorta/metabolismo , Miocárdio/metabolismo , Oxirredução , Estresse Oxidativo , Condicionamento Físico Animal/fisiologia , Adolescente , Adulto , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Criança , Feminino , Humanos , Masculino , Carbonilação Proteica , Ratos , Superóxido Dismutase/metabolismo , Tiobarbitúricos/metabolismoRESUMO
Vitamin A exerts a wide range of physiological roles from embryonic to adulthood stages of the mammalian life. However, there is a great concern regarding the deleterious effects of vitamin A use even therapeutically. It was shown that vitamin A induces behavioral impairments, for instance, anxiety-like behavior and depression, in experimental animals and humans. Caspases are enzymes associated with cell death; however, there is a role for such enzymes also in synaptic plasticity. Then, based on previously published data, we have investigated the effects of vitamin A supplementation at clinical doses (1000-9000 IU/kg/day) for 28 days on caspase-3 and caspase-8 activities in adult rat cerebral cortex, cerebellum, striatum, and hippocampus. Furthermore, we have quantified TNF-alpha levels, a pro-inflammatory cytokine that, besides other biological roles, trigger the extrinsic apoptotic pathway in several cellular types, in those rat brain regions. Interestingly, we found increased caspase-3 activity only in rat cerebral cortex. In all the other regions caspase-3 and caspase-8 activities did not change, as well as the levels of TNF-alpha. The presented results, herein, indicate that more caution is needed regarding vitamin A clinical use and, also importantly, the consumption of vitamin A-fortified foods, which are not exclusively distributed among vitamin A-deficient subjects.
Assuntos
Caspase 3/metabolismo , Córtex Cerebral/efeitos dos fármacos , Vitamina A/análogos & derivados , Vitaminas/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Caspase 8/metabolismo , Córtex Cerebral/enzimologia , Córtex Cerebral/patologia , Diterpenos , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Ésteres de Retinil , Fator de Necrose Tumoral alfa/metabolismo , Vitamina A/administração & dosagem , Vitamina A/efeitos adversos , Vitamina A/farmacologia , Vitaminas/administração & dosagem , Vitaminas/farmacologiaRESUMO
Vitamin A is a micronutrient involved in the regulation of a normal mammalian brain function. In spite of this, it has been demonstrated that vitamin A exerts a wide range of deleterious effects regarding neuronal homeostasis, for instance impairing brain metabolism and suppressing neurogenesis, to cite a few. In addition, vitamin A is a redox active molecule, i.e. it is both anti- and pro-oxidant, depending on its concentration. In the herein presented work, we performed some experiments aiming to investigate the effects of clinically applied doses of vitamin A (1000-9000 IU/kg/day during 28 days) on rat hypothalamic redox state and mitochondrial electron transfer chain (METC) activity, as well as on hypothalamic alpha-synuclein and D2 receptor (dopamine receptor) contents. Additionally, we quantified caspase-3 activity and tumor necrosis factor-alpha (TNF-alpha) levels to assess either neuronal death or an inflammatory state in such brain area. We found that vitamin A supplementation increased free radical production, as well as oxidative and nitrosative stress, in rat hypothalamus. Also, we observed increased complex I-III activity, but decreased complex IV activity in the hypothalamus of vitamin A-treated rats, which may give rise to the increased superoxide anion (O(2)(-)) production found here. Other parameters investigated here, i.e. alpha-synuclein and D2 receptor contents did not change. Even though we did not observe signs of increased cell death or inflammation in the rat hypothalamus, more attention is needed when vitamin A is the choice of treatment in certain pathologies.
Assuntos
Hipotálamo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Vitamina A/administração & dosagem , Administração Oral , Animais , Encéfalo/metabolismo , Caspase 3/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Hipotálamo/química , Hipotálamo/metabolismo , Oxirredução , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/análise , alfa-Sinucleína/metabolismoRESUMO
Vitamin A, beyond its biological role, is an alternative choice in treating some life threatening pathologies, for instance leukemia and immunodeficiency. On the other hand, vitamin A therapy at moderate to high doses has caused concern among public health researchers due to the toxicological aspect resulting from such habit. It has been described hepatotoxicity, cognitive disturbances and increased mortality rates among subjects ingesting increased levels of vitamin A daily. Then, based on the previously reported data, we investigated here receptor for advanced glycation endproducts (RAGE) immunocontent and oxidative damage levels in cerebral cortex of vitamin A-treated rats at clinical doses (1,000-9,000 IU/kg day(-1)). RAGE immunocontent, as well as oxidative damage levels, were observed increased in cerebral cortex of vitamin A-treated rats. Whether increased RAGE levels exert negative effects during vitamin A supplementation it remains to be investigated, but it is very likely that deleterious consequences may arise from such alteration.
Assuntos
Córtex Cerebral/metabolismo , Receptores Imunológicos/metabolismo , Vitamina A/farmacologia , Animais , Western Blotting , Caspase 8/metabolismo , Córtex Cerebral/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Masculino , Carbonilação Proteica , Ratos , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa , Tirosina/análogos & derivados , Tirosina/análise , Tirosina/metabolismoRESUMO
It is well known that antioxidants play an important role in sperm fertility, but there is no data on the literature regarding the effect of male chemical cues in the antioxidant defenses of the female reproductive tract. Here, we evaluated oxidative parameters in ovaries and uterus of virgin female rats isolated from contact to males and exposed only to male-soiled bedding (MSB). Four-month-old Wistar (regular 4-day cyclic) virgin female rats were utilized from proestrus to estrus phase of the reproductive cycle for experimental exposure. In an isolated room, female rats were exposed for 90 min to MSB. For biochemical assays, female rats were killed by decapitation at 30, 90, 180, and 240 min after the end of exposure, and the ovaries and uterus were removed for further analysis. Antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), the nonenzymatic antioxidant potential (total radical-trapping antioxidant parameter), and the oxidative damage parameters (thiobarbituric acid-reactive species and carbonyl content) were analyzed. We observed an increase in the nonenzymatic antioxidant potential and diminished free radical oxidative damage in uterine tissue, 30 and 90 min after exposure. Furthermore, in ovaries, enzymatic defenses were modulated distinctly along the 240 min after exposure. MSB exposure modulates the antioxidant profile in ovaries and uterus of receptive female rats. It is possible that the modifications in the oxidative profile of the female genital tract may have important implications in the process of fertilization.
Assuntos
Antioxidantes/metabolismo , Ovário/metabolismo , Peroxidases/metabolismo , Reprodução/fisiologia , Útero/metabolismo , Animais , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de TempoRESUMO
Vitamin A at moderate to high doses is applied in the treatment of some life threatening pathological conditions, for instance cancers. Additionally, vitamin A at low concentrations is a known antioxidant molecule. However, by increasing vitamin A (or its derivatives) concentrations, there is an increase in the levels of oxidative stress markers in several experimental models. Furthermore, it was reported that vitamin A therapy at high doses might induce cognitive decline among the patients, which may become anxious or depressive, for example, depending on vitamin A levels intake. We have previously reported increased levels of oxidative stress markers in rat substantia nigra and striatum. However, the mechanism by which this vitamin altered the redox environment in such rat brain regions remains to be elucidated. In the herein presented work, we have investigated the effects of vitamin A supplementation at clinical doses (1000-9000 IU/kg day(-1)) for 28 days on rat substantia nigra and striatum mitochondrial electron transfer chain (METC) activity, which may produce superoxide anion radical (O(2)(-*)) when impaired. Additionally, the levels of non-enzymatic antioxidant defenses were evaluated, as well as 3-nitrotyrosine, alpha- and beta-synucleins and TNF-alpha levels through ELISA assay. We observed impaired METC in both rat brain regions. Moreover, we found increased O(2)(-*) production and nitrotyrosine content in the nigrostriatal axis of vitamin A-treated rats, suggesting that the use of vitamin A at therapeutic doses may be rethought due to this toxic effects found here.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neostriado/metabolismo , Receptores de Dopamina D2/metabolismo , Substância Negra/metabolismo , Tirosina/análogos & derivados , Vitamina A/uso terapêutico , Vitaminas/uso terapêutico , alfa-Sinucleína/metabolismo , Animais , Caspase 3/metabolismo , Suplementos Nutricionais , Transporte de Elétrons/efeitos dos fármacos , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Sequestradores de Radicais Livres/farmacologia , Glutationa Transferase/metabolismo , Indicadores e Reagentes , Neostriado/efeitos dos fármacos , Oxirredução , Ratos , Receptores de Dopamina D2/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/metabolismoRESUMO
Chemical cues are widely used for intraspecific social communication in a vast majority of living organisms ranging from bacteria to mammals. As an example, mammals release olfactory cues with urine that promote neuroendocrine modulations with changes in behavior and physiology in the receiver. In this work, four-month-old Wistar (regular 4-day cyclic) virgin female rats were utilized in the proestrus-to-estrus phase of the reproductive cycle for experimental exposure. In an isolated room, female rats were exposed for 90 min to male-soiled bedding (MSB). Elevated plus-maze assay, open field test, and light/dark box task were performed to analyze behavioral alterations on females after exposure. For biochemical assays, female rats were killed and the hypothalamus, hippocampus, and frontal cortex were isolated for further analysis. Antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), non-enzymatic antioxidant defense measurements (TRAP and TAR), and the oxidative damage parameters (TBARS, Carbonyl and SH content) were analyzed. In behavioral analyses we observe that female rats show decreased anxiety and locomotory/exploratory activities after MSB exposure. In biochemical assays we observed an increase in both enzymatic and non-enzymatic antioxidant defenses in different central nervous system (CNS) structures analyzed 30 and 90 min after MSB exposure. Furthermore, hippocampus and frontal cortex showed diminished free radical oxidative damage at 180 and 240 min after exposure. These results provide the first evidence that oxidative profile of female CNS structures are altered by chemical cues present in the MSB, thus suggesting that pheromonal communication is able to modulate radical oxygen species production and/or clearance in the female brain.
Assuntos
Antioxidantes/metabolismo , Sinais (Psicologia) , Comportamento Exploratório , Lobo Frontal/metabolismo , Hipocampo/metabolismo , Hipotálamo/metabolismo , Atividade Motora , Comportamento Sexual Animal , Animais , Ansiedade , Feminino , Masculino , Ratos , Ratos WistarRESUMO
There is a growing body of evidence showing that vitamin A induces toxic effects in several experimental models and in human beings. In the present work, we have investigated the effects of short-term vitamin A supplementation on the adult rat liver redox status. We have found that vitamin A at therapeutic doses induces a hepatic oxidative insult. Furthermore, we have observed increased antioxidant enzyme activity in the liver of vitamin-A-treated rats. Additionally, some mitochondrial dysfunction was found since superoxide anion production was increased in vitamin-A-treated rat liver submitochondrial particles, which may be the result of impaired mitochondrial electron transfer chain activity, as assessed here. We have also isolated rat liver mitochondria and challenged it with 75 muM CaCl2, a non-oxidant agent that is able to induce mitochondrial oxidative stress indirectly. We have found that mitochondria isolated from vitamin-A-treated rat liver are more sensitive to CaCl2 than control mitochondria regarding the redox status. Importantly, vitamin A seems to alter mitochondrial redox status independently of the participation of the mitochondrial permeability transition pore, which is activated by Ca2+ ions since cyclosporin A did not prevent the oxidative insult elicited by Ca2+ addition. Overall, we show here that mitochondria are a target of vitamin-A-associated toxicity also in vivo.
Assuntos
Cálcio/metabolismo , Mitocôndrias Hepáticas , Oxirredutases/metabolismo , Vitamina A , Animais , Cálcio/farmacologia , Ciclosporina/farmacologia , Transporte de Elétrons , Metabolismo Energético/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Poro de Transição de Permeabilidade Mitocondrial , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Partículas Submitocôndricas/metabolismo , Superóxidos/metabolismo , Vitamina A/administração & dosagem , Vitamina A/efeitos adversosRESUMO
Vitamin A and its derivatives, the retinoids, exert modulatory roles on central nervous system (CNS) function. However, the clinical use of vitamin A at moderate to high doses induces serious side effects, including dysfunctional brain metabolism and mood disorders. Then, we have investigated in this work the effects of vitamin A supplementation at 1000, 2500, 4500, or 9000IU/kg/day for 28 days on redox and bioenergetics parameters in adult rat frontal cortex. Additionally, we have measured caspase-3 and caspase-8 activities to analyze whether vitamin A supplementation as retinol palmitate induces neuronal death in such brain area. The levels of the pro-inflammatory cytokine TNF-alpha were also quantified. We have found increased rates of O(2)(-) production and increased levels of markers of oxidative insult in frontal cortex and also in mitochondrial membranes. Superoxide dismutase (SOD) enzyme activity was increased, and catalase (CAT) enzyme activity did not change in this experimental model. Surprisingly, we observed increased mitochondrial electron transfer chain (METC) activity. Caspase-3 and caspase-8 activities and TNF-alpha levels did not change in this experimental model. Finally, vitamin A supplementation did not induce depression in adult rats after 28 days of treatment. However, exploration in the center of an open field was decreased and time spent in freezing behavior was increased in vitamin A treated rats.