Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats

Abstract

Objectives:To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Methods: Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/ nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. Results: MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. Conclusions: NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress. Arq Bras Endocrinol Metab. 2010;54(6):530-9 Keywords Oxidative stress; diabetes; nitric oxide; vascular function; N-acetylcysteine RESUMO Objetivos: Verificar se um modelo experimental de diabetes por aloxana promove estresse oxidativo, reduz a disponibilidade de óxido nítrico e causa disfunção vascular, e avaliar o efeito da N-acetilcisteína (NAC) nesses parâmetros. Métodos: Ratos diabéticos por aloxana foram tratados com NAC por quatro semanas. Níveis plasmáticos de malondialdeído (MDA) e nitrito/ nitrato (NOx), imunomarcação para óxido nítrico sintase endotelial e induzida (eNOS e iNOS) e reatividade vascular da aorta foram comparados entre ratos diabéticos (D), diabéticos tratados (TD) e controles (C). Resultados: O MDA aumentou nos grupos D e TD. O NOx não diferiu entre os grupos. A marcação da eNOS no endotélio reduziu e a da iNOS na adventícia aumentou nos grupos D e TD. A responsividade dos anéis vasculares à acetilcolina, nitroprussiato de sódio e fenilefrina não diferiu entre os grupos. Conclusões: A NAC não teve efeito sobre os parâmetros avaliados. Esse modelo experimental não promoveu disfunção vascular apesar do desenvolvimento de estresse oxidativo. Arq Bras Endocrinol Metab. 2010;54(6):530-9 Descritores

The Hypoglycemic Effect of the Kelp on Diabetes Mellitus Model Induced by Alloxan in Rats

“…The “common soil” theory of Ceriello et al [15,16] holds that oxidative stress is a common feature of insulin resistance, diabetes mellitus and cerebrovascular diseases [17]. In a body suffering from various harmful stimuli, there is an increase in free radicals and decreased elimination of those radicals can upset the balance of the oxidation system and antioxidant system, and damage tissues and function [18,19].…”

Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy

“…[27] Treatment with SMC showed improvement in the myelination and degenerative changes of the nerve fiber in both the groups. Even though a complete restoration of neuronal integrity is not evident, a delay in the progression of diabetic neuropathy is obvious under the action of the SMC.…”

Treatment with N-acetylcysteine does not alter blood glucose levels and the oxidative stress status in diabetic rats

“…Some studies have shown that NAC treatment is able to decrease the MDA levels in diabetes. [11,20,32] However, Capellini et al, [29] did not find a positive result with regard to the MDA levels after NAC supplement [Values are means ± S.E from five animals/group; *P < 0.05 as compared to control/saline group, **P < 0.05 as compared to diabetic/ saline group in diabetes. In our study, the plasma levels of MDA were not altered in diabetic rats treated with NAC, as shown in the Table 4.…”

“…[29] Possibly the destruction of pancreatic beta cells by alloxan-induced ROS generation [19] hindered the potentially therapeutic effect of NAC on these cells, and consequently on the hyperglycemia status. In this aspect, perhaps the injection of NAC simultaneously with alloxan, in rats, prevents necrosis of pancreatic beta cells caused by ROS generation, [30] allowing for the proper functioning of the pancreas, and hence, insulin release.…”

“…[14] Possibly these diabetic rats had impaired glutathione synthesis due to decreased gamma-glutamylcysteine synthetase activity, as was described by others studies. [29,38] Patriarca et al, [39] showed that the failure of NAC in the re-establishment of GSH levels could be attributed to the unbalanced ratio between GSH synthesis and consumption, where the high consumption rate could lower GSH, even in the presence of the substrate for the synthesis. Furthermore, poor conversion of NAC to cysteine, excess urinary NAC, and decreased uptake of plasma cysteine by red blood cells could be the cause for the lack of effect of NAC on the GSH levels in a diabetic state.…”