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1.
Metab Brain Dis ; 36(4): 685-699, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33555496

RESUMO

Citrullinemia Type I is an inborn error, which leads to accumulation of citrulline and ammonia in blood and body tissues. We evaluated the in vitro effects of citrulline, ammonia and the influence of resveratrol on oxidative stress parameters in the cerebrum of 30- and 60-day-old male Wistar rats. Citrulline (0.1, 2.5, 5.0 mM), ammonia (0.01, 0.1, 1.0 mM) and resveratrol (0.01, 0.1, 0.5 mM) were added to the assays to measure thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Citrulline (2.5 and 5.0 mM) increased TBA-RS in the cerebellum of 30-day-old and in the cerebral cortex and cerebellum of 60-day-old. Citrulline (5.0 mM) increased SOD and reduced GSH-Px in the hippocampus of 30-day-old, whereas in the cerebellum it increased GSH-Px. In the cerebral cortex, 2.5 and 5.0 mM citrulline reduced GSH-Px. In 60-day-old, 2.5 and 5.0 mM citrulline increased SOD in the cerebellum, increased GSH-Px in the cerebral cortex and 5.0 mM citrulline reduced CAT and increased SOD in the cerebral cortex. Ammonia (0.1 and 1.0 mM) reduced the sulfhydryl content in the cerebral cortex of 30- and 60-day-old, 1.0 mM ammonia increased SOD and reduced GSH-Px in the cerebellum of 30-day-old and increased SOD in the hippocampus and cerebellum of 60-day-old. Resveratrol was able to prevent the majority of these alterations. Thus, citrulline and ammonia induce oxidative stress in the cerebrum of rats; however, resveratrol was able to exert antioxidant effects against these substances.


Assuntos
Antioxidantes/farmacologia , Encéfalo/metabolismo , Citrulinemia/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/fisiologia , Resveratrol/farmacologia , Amônia/toxicidade , Animais , Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Citrulina/toxicidade , Citrulinemia/induzido quimicamente , Citrulinemia/prevenção & controle , Relação Dose-Resposta a Droga , Masculino , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Resveratrol/uso terapêutico
2.
Naunyn Schmiedebergs Arch Pharmacol ; 394(5): 873-884, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33205249

RESUMO

We investigated the in vitro effects of citrulline (0.1, 2.5 and 5.0 mM) and ammonia (0.01, 0.1 and 1.0 mM), and the influence of resveratrol (0.01 mM, 0.1 mM and 0.5 mM) on pyruvate kinase, citrate synthase, succinate dehydrogenase (SDH), complex II, and cytochrome c oxidase activities in cerebral cortex, cerebellum and hippocampus homogenates of 60-day-old male Wistar rats. Results showed that 2.5 and 5.0 mM citrulline decreased pyruvate kinase activity in cerebral cortex and, at a concentration of 5.0 mM, increased its activity in hippocampus. Additionally, 5.0 mM citrulline increased citrate synthase activity in the cerebellum of rats. Citrulline (5.0 mM) reduced complex II and cytochrome c oxidase activities in cerebral cortex and hippocampus. With regard to ammonia, at 0.1 and 1.0 mM, decreased complex II activity in cerebral cortex and at 1.0 mM decreased its activity in cerebellum and hippocampus. Ammonia (1.0 mM) also decreased cytochrome c oxidase activity in cerebral cortex and cerebellum of rats. Resveratrol was able to prevent most of the alterations caused by these metabolites in the biomarkers of energy metabolism measured in the cerebrum of rats. Data suggest that these alterations in energy metabolism, caused by citrulline and ammonia, are probably mediated by the generation of free radicals, which can in turn be scavenged by resveratrol.


Assuntos
Citrulinemia/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Resveratrol/farmacologia , Amônia/administração & dosagem , Amônia/toxicidade , Animais , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Citrulina/administração & dosagem , Citrulina/toxicidade , Citrulinemia/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Resveratrol/administração & dosagem
3.
Bol. latinoam. Caribe plantas med. aromát ; 20(2): 132-146, 2021. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1342208

RESUMO

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.


Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.


Assuntos
Animais , Masculino , Ratos , Extratos Vegetais/administração & dosagem , Myrtaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Cloreto de Metileno/administração & dosagem , Glicemia/efeitos dos fármacos , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Ratos Wistar , Estreptozocina , Estresse Oxidativo/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Compostos Fenólicos/análise , Hipolipemiantes/administração & dosagem , Antioxidantes/administração & dosagem
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