RESUMO
We investigated the in vitro and in vivo effects of arginine (Arg) on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in renal tissues of rats. We also studied the influence of antioxidants (α-tocopherol plus ascorbic acid) and nitric oxide synthase inhibitor NG -nitro-l-arginine methyl ester (l-NAME) on the effects elicited by Arg. Results showed that Arg in vitro (1.5 mM) decreased SOD activity and increased the levels of TBA-RS in the renal medulla. Acute administration of Arg [0.8 g/kg, intraperitoneal injection] decreased CAT activity, increased SOD activity and TBA-RS levels in the renal medulla, and decreased CAT activity in the renal cortex of rats. Most results were prevented by antioxidants and/or l-NAME. Data indicate that Arg causes an oxidative imbalance in the renal tissues studied; however, in the presence of antioxidants and l-NAME, some of these alterations in oxidative stress were prevented.
Assuntos
Antioxidantes/farmacologia , Hiperargininemia/prevenção & controle , Rim/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo/efeitos dos fármacos , alfa-Tocoferol/farmacologia , Animais , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Hiperargininemia/induzido quimicamente , Hiperargininemia/metabolismo , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
In the present investigation, we initially evaluated the in vitro effect of N-acetylarginine on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of rats. Results showed that N-acetylarginine, at a concentration of 5.0 µM, decreased the activity of CAT in erythrocytes, enhanced TBA-RS in the renal cortex, decreased CAT and SOD activities in the renal medulla and decreased CAT and increased SOD and GSH-Px activities in the liver of 60-day-old rats. Furthermore, we tested the influence of the antioxidants, trolox and ascorbic acid, as well as of the N(ω) -nitro-L-arginine methyl ester (L-NAME) on the effects elicited by N-acetylarginine on the parameters tested. Antioxidants and L-NAME prevented most of the alterations caused by N-acetylarginine on the oxidative stress parameters evaluated. Data indicate that oxidative stress induction is probably mediated by the generation of NO and/or ONOO(-) and other free radicals because L-NAME and antioxidants prevented the effects caused by N-acetylarginine in the blood, renal tissues and liver of rats. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by N-acetylarginine.
Assuntos
Arginina/análogos & derivados , Hiperargininemia/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Vitaminas/farmacologia , Animais , Antioxidantes/farmacologia , Arginina/metabolismo , Arginina/farmacologia , Ácido Ascórbico/farmacologia , Cromanos/farmacologia , Córtex Renal/metabolismo , Medula Renal/metabolismo , Fígado/metabolismo , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , alfa-Tocoferol/farmacologiaRESUMO
BACKGROUND AND PURPOSE: Hyperargininemia (HA) is a rare autosomal recessive metabolic disorder and the neuroimaging features of this disease have seldom been reported. Hyperammonemic encephalopathy is uncommon in HA, and the clinical presentation of HA is distinct from other urea cycle disorders. This paper describes the brain MRI findings and a magnetic resonance spectroscopy (MRS) study of a series of Brazilian HA patients. METHODS: Brain MR images were obtained in eight male and two female patients with the classic HA phenotype. Six patients were evaluated twice. Single-voxel (1)H-MRS was also performed in six of the patients. RESULTS: Only 1 patient, with less severe neurological symptoms, had normal MRI images. A variable degree of cerebral atrophy was noted in the other patients, and 3 patients also presented mild symptoms of cerebellar atrophy. MRS indicated no metabolic abnormalities in any patient. CONCLUSIONS: We present the MRI and MRS findings of a large series of HA patients. Variable degrees of brain atrophy and mild cerebellar atrophy were observed, and these findings were not specific. No metabolic abnormality was observed using MRS in this series of patients.
Assuntos
Arginina/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Hiperargininemia/diagnóstico , Hiperargininemia/metabolismo , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Atrofia , Biomarcadores/metabolismo , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
1. We have previously demonstrated that arginine administration induces oxidative stress and compromises energy metabolism in rat hippocampus. In the present study we initially investigated the influence of pretreatment with alpha-tocopherol and ascorbic acid on the effects produced by arginine on hippocampus energy metabolism. We also tested the effect of acute administration of arginine on various parameters of energy metabolism, namely glucose uptake, lactate release and on the activities of succinate dehydrogenase, complex II and cytochrome c oxidase in rat cerebellum, as well as the influence of pretreatment with alpha-tocopherol and ascorbic acid on the effects elicited by arginine on this structure. 2. Sixty-day-old female Wistar rats were treated with a single i.p. injection of saline (control) or arginine (0.8 g/kg) and were killed 1 h later. In another set of experiments, the animals were pretreated for 1 week with daily i.p. administration of saline (control) or alpha-tocopherol (40 mg/kg) and ascorbic acid (100 mg/kg). Twelve hours after the last injection of the antioxidants the rats received one i.p. injection of arginine (0.8 g/kg) or saline and were killed 1 h later. 3. Results showed that arginine administration significantly increased lactate release and diminished glucose uptake and the activities of succinate dehydrogenase and complex II in rat cerebellum. In contrast, complex IV (cytochrome c oxidase) activity was not changed by this amino acid. Furthermore, pretreatment with alpha-tocopherol and ascorbic acid prevented the impairment of energy metabolism caused by hyperargininemia in cerebellum and hippocampus of rats.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Metabolismo Energético/efeitos dos fármacos , Hipocampo , Hiperargininemia/metabolismo , alfa-Tocoferol/farmacologia , Animais , Antioxidantes/administração & dosagem , Arginina/administração & dosagem , Arginina/farmacologia , Ácido Ascórbico/administração & dosagem , Complexo II de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Glucose/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ácido Láctico/metabolismo , Ratos , Ratos Wistar , Succinato Desidrogenase/metabolismo , alfa-Tocoferol/administração & dosagemRESUMO
Hyperargininemia is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of arginine and clinically by severe neurological symptoms whose pathophysiology is poorly understood. In the present study we investigated the effect of arginine administration on the antioxidant enzyme activities catalase, glutathione peroxidase and superoxide dismutase in rat midbrain. We also tested the effect of L-NAME on the effects produced by Arg. The results showed that arginine decreased catalase activity, without altering the other two activities. L-NAME had no effect on catalase activity, but prevented the reduction of this enzyme provoked by arginine, suggesting that NO formation is involved in the reduction of catalase activity caused by the amino acid. If these findings also occur in the human condition, it may be presumed that oxidative stress contributes to the brain dysfunction observed in hyperargininemia.
Assuntos
Arginina/farmacologia , Catalase/metabolismo , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/enzimologia , Animais , Inibidores Enzimáticos/farmacologia , Glutationa Peroxidase/metabolismo , Hiperargininemia/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the cerebral cortex of rats in the presence of various concentrations of these compounds. The results showed that all guanidino compounds tested significantly increased chemiluminescence and decreased TRAP at concentrations similar to those observed in the tissue of hyperargininemic patients. Furthermore, these compounds inhibited CAT and GSH-Px activities to varying extents, with GSH-Px activity being more susceptible to their action. In turn, argininic acid inhibited all enzyme activities, and its main action was also directed towards GSH-Px. The results suggest that oxidative stress caused by guanidino compounds may be involved in the brain dysfunction amongst other potential pathophysiological mechanisms observed in hyperargininemia.