Correlations between Endothelial Functions and ROS Detection in Diabetic Microvascular Wall:Early and Late Ascorbic Acid Supplementation

Pattarin Sridulyakul,Suthiluk Patumraj,Natchaya Wongeak-In

doi:10.1155/2012/709695

Pattarin Sridulyakul, Suthiluk Patumraj + Show 1 more

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https://doi.org/10.1155/2012/709695

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Abstract

The correlation between endothelial function and reactive oxygen species detecting from diabetic microvascular wall and the antioxidant effect of ascorbic acid (AA) during early and late phases of diabetic induction were determined. Male Spraque-Dawley rats were divided into four groups: control, diabetes rats (DM, using iv.injection of 55 mg/kg BW streptozotocin, (STZ)), and two groups of DM rats treated with AA (1 g/L, (STZ)) starting on day 2 (DM + AAday2) and week 6th (DM + AA6wk). On 12th week after STZ injection, the findings showed that in DM group, Ach (10−5 M)-induced vasodilatation was decreased, while the number of leukocyte adhesion was increased significantly (P < 0.01). Interestingly, these abnormalities induced by DM could be protected or improved in both AA-treated groups, DM + AAday2 and DM + AA6wk. By using dihydrorhodamine 123, our findings also indicated that the existing of ROS productions on diabetic arteriolar and venular walls were different significantly (ROSarteriole = 165.89 ± 24.59 and ROSvenule = 172.26 ± 34.70) (P < 0.05). Moreover by using BH4 inhibitor to induce increase in arteriolar ROS, the results also confirmed that AA could improve endothelial function with closed correlation to its potential to reduce vascular ROS content.

Highlights

The imbalance between hyperglycemic-induced reactive oxygen species (ROS) and antioxidative systems both enzymatic and nonenzymatic appears to be a major factor contributed to several diabetic complications [1,2,3,4,5,6]
Loss of body weight was observed in all of three DM groups, DM, DM + AAday2, and DM + AA6wk, as compared to their aged-match controls. In both DM + AAday2, and DM + AA6wk groups, the blood glucose and HbA1C were not significantly different when compared to the DM rats, while ascorbic acid (AA) supplementation increased the body weight significantly (P < 0.001) (Table 1)
The ROS-sensitive fluorescent probe dihydrorhodamine 123 (DHR)-123 could detect in vivo ROS and was used successfully by several other mesenteric studies [12,13,14]

Summary

Introduction

The imbalance between hyperglycemic-induced reactive oxygen species (ROS) and antioxidative systems both enzymatic and nonenzymatic appears to be a major factor contributed to several diabetic complications [1,2,3,4,5,6]. It has been suggested that the diabetes-induced oxidative stress is a crucial factor contributing to endothelial cell dysfunction. Many studies have shown close correlation between diabetes-induced ROS and impairments of both endothelial functions at arterioles and venules in the microcirculation. In both human and animal diabetic models, two characters which are commonly used as indicators of endothelial cell dysfunction are the impairment of endothelium-dependent vascular relaxation and the increase in leukocyte-endothelial cell interaction [4,5,6,7,8,9]. The decrease of nitric oxide (NO) bioavailability is referred as the underlining cause of those impairments [5, 9]

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