RESUMO
AIM: The effects of the inhibition of nitrosative stress by aminoguanidine in an experimental model of diabetes mellitus (DM) were investigated. METHODS: Twenty-one male Wistar rats were divided into three groups: control (CO), diabetic (DM), and diabetic treated with aminoguanidine (DM+AG). Aminoguanidine (aminoguanidine hemisulfate salt, Sigma Chemical Co., St. Louis, MO, USA) was used at a dose of 50 mg/kg (i.p.) during the last 30 days of the experiment. The expression levels of liver lipoperoxidation (TBARS - nmol/mg protein), inducible oxide nitric synthase (iNOS), nitrotyrosine and the NFκB nuclear transcription factor p65 were examined using western blot analysis. RESULTS: The DM group demonstrated an increase in lipoperoxidation and in the expression of iNOS, nitrotyrosine and p65. Aminoguanidine reduced hepatic lipid peroxidation and protein expression levels of iNOS, nitrotyrosine and p65. CONCLUSION: Aminoguanidine treatment reduces liver oxidative and nitrosative stress in diabetic animals. In addition, aminoguanidine reduced the expression of p65 in the liver.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Guanidinas/uso terapêutico , Fígado/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Nitrogênio/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
AIM: To investigate the effects of exogenous antioxidant copper zinc superoxide dismutase (Cu/Zn SOD) on oxidative stress in the experimental model of diabetes mellitus (DM). METHODS: Twenty eight male Wistar rats divided in four groups were used: control (CO), controls treated with SOD (CO + SOD), diabetics (DM), and diabetics treated with SOD (DM + SOD). SOD (orgotein, 13 mg/Kg body weight was administered. DM was induced by a single streptozotocin injection (i.p., 70 mg/kg), and 60 days later, we evaluated liver oxidative stress. RESULTS: Liver lipoperoxidation was increased in the DM group and significantly decreased in the DM + SOD group. Nitrite and nitrate measures were reduced in the DM and increased in the DM + SOD group, while iNOS expression in the DM group was 32% greater than in the CO and 53% greater in the DM + SOD group than in the DM group (P < .01). P65 expression was 37% higher in the DM (P < .05), and there was no significant difference between the DM and DM + SOD groups. CONCLUSION: SOD treatment reduced liver oxidative stress in diabetic animals, even though it did not change NFκB. SOD also increased NO, probably by the increased dismutation of the superoxide radical. The iNOS expression increase, which became even more evident after SOD administration.