Diabetes mellitus is a chronic, systemic, metabolic disease defined by hyperglycemia and characterized by alterations in the metabolism of carbohydrate, protein and lipid. Oxidative stress thought to be increased in a system where the rate of free radical production is increased and/or the antioxidant mechanisms are impaired. In recent years, the oxidative stress-induced free radicals have been implicated in the pathology of IDDM [14
The present study was examined the changes in both extra and intracellular antioxidants and oxidant status in a children suffering from IDDM. The diabetic children were treated with insulin and yet they were hyperglycemic. Prolonged exposure to hyperglycemia and consequent non-enzymatic posttranslational modification of proteins resulting from chemical reaction between glucose and primary amino groups of proteins – glycation, and also increased oxygen free radicals through auto oxidation of glucose [15
]. Our results are in accordance with those of previous finding clearly show the increased glucose levels induces diabetes, the overproduction of oxygen free radicals and consequently increases the protein oxidation and lipid oxidation (table ). Plasma MDA and PCG levels were significantly higher, which would indicate that free radical mediated oxidative damage of lipids and proteins is produced at in diabetics [35
]. To our knowledge, there are no reports in the literature concerning plasma PCG levels in IDDM patients in relation with antioxidant status. Carbonyl group formation is considered an early and stable marker for protein oxidation. Oxidized proteins constitute a substantial fraction of the catalytically inactive or less active forms of enzymes, which may have direct metabolic consequences [37
]. According to Gliesner et al [35
] showed no statistically significant differences were found for any of the oxidative stress markers (PCG) assessed between patients with DM1 and controls. In addition, weight, height, and routine metabolic tests, including creatininemia and cholesterol levels, were similar between the groups. The lack of significant differences between healthy controls and patients with DM1 suggested that treatment is able to counteract the increase in free radical production. Ahmed et al [41
] observed profound increases in proteolytic products of glycated and oxidised proteins in diabetic patients, concurrent with much lower increases in protein glycation and oxidation adduct residues.
Nitric oxide (NO) is an important vascular target for ROS. Superoxide neutralizes NO, and the peroxynitrite formed is a source of hydroxyl radicals that can cause endothelial damage [43
]. Increased levels of nitric oxide were observed in Type I DM (table ). Astaneie et al [44
] have shown the elevated levels of NO with total antioxidant power. Existence of increased total antioxidant power in the presence of normal lipid peroxidation in plasma of type I diabetic patients indicates the existence of oxidative stress. Oxidative stress therefore diminishes vessel endothelium-dependent relaxation, which is apparent in some experimental preparations even after acute exposure to hyperglycemia. Defective endothelium-dependent relaxation has been observed in chronic diabetic animals, and also in type 1 and type 2 diabetic subjects [41
] and is an important potential target for antioxidant treatment.
The relationship between hyperglycemia and oxygen free radicals is supported by our results demonstrating an association between blood levels of glucose and enzymatic oxidants such as super oxide dismutase and glutathione peroxidase, only in children with IDDM (table ). The decreased erythrocyte Cu/Zn-SOD and catalase activity in our young diabetic patients also supports the hypothesis of radical mediated injury in this disease. These results are in agreement with others [47
]. Circulating RBC act as a sink for free radicals. Consequently, erythrocytes are subject to a continuous flux of O2
. It is, therefore, possible that SOD may have an important physiological role in combating this process, since this enzyme can catalyze the dissimulation of two super oxide radicals into H2
. In the present study, on native PAGE, the plasma concentration of ceruloplasmin in IDDM was significantly lower than those of controls. These results are in agreement with others [50
] who reported a significant reduction in the plasma concentration of ceuloplasmin in type I diabetic patients. It has been reported that ceruloplasmin is immunologically altered with decrease in enzymatic oxidants. These results may explain the significant reduction in SOD activity in IDDM patients, since increased H2
and decreased ceruloplasmin [51
]. Selenium-dependent glutathione peroxidase (GPx), which works in parallel with SOD, protects cell proteins and cell membranes against oxidative damage. In the present sudy, the GPx activity was decreased significantly compared to that of the controls and a negative correlation coefficient between GPx activity and blood glucose concentration was observed in these children (table ). However, in the published lieterature, the GPx response to diabetes has been conflicting. Diabetics have been reported to be associated with increased [48
] decreased [53
] or unchanged [54
]. In lieu with GPx, the catalase activities were also decreased in diabetes compared to control subjects (table ). The low GPx activity could be directly explained by either low GSH content or enzyme inactivation under sever oxidative stress.
In addition to antioxidant enzyme activities, the capacity of the antioxidant system to cope with or trap the free radicals generated under normal or pathological conditions was evaluated by measuring the level of total antioxidant status. It reflects the status of α-tocopherol, vitamin A, β-carotene, ascorbic acid, albumin, uric acid and other antioxidants [42
]. These extracellular nonenzymatic antioxidants delay or inhibit the oxidative process. Enhanced lipid peroxidation increases the need for lipid soluble antioxidants, such as α-tocopherol and vitamin A and β-carotene. A significance difference in the mean plasma concentration of total antioxidant status was observed in IDDM patients (table ). Low levels of vitamin E are associated with increased incidence of diabetes and some research suggests that people with diabetes have decreased levels of antioxidants [32
]. People with diabetes may also have greater antioxidant requirements because of increased production of free radicals in hyperglycemia [56
]. The results of Martin-Gallan et al [42
] clearly show systemic peroxidative damage associated with insufficient defense mechanisms against ROS to be already present at clinical onset of type 1 diabetes mellitus in children and adolescents. The present study has also demonstrated a significantly lower plasma ascorbate children compared with their controls. A significant negative correlation coefficient between blood glucose and vitamin C has been observed. Patients with diabetes or the metabolic syndrome have low levels of the antioxidant vitamin C [58
] and also control the diabetes [33
]. Chen et al [59
] shown that high-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance.
The findings of the present study suggest that diabetes in an altered metabolic state of oxidation-reduction and that it is convenient to give therapeutic interventions with antioxidants. The loss of antioxidant capacity is statistically associated with accelerated aging processes in diabetic patients, due to an increase in basal oxidation products of etrythrocytes associated with monosaccharide autooxidative glycation [4
]. Our present work takes into account the hypothesis involving the relation between individual components in the intact clinical model and the complex oxidant-antioxidant plasmatic systemic balance. We clearly identified antioxidant markers that were affected in the presence of IDDM; include SOD, plasma albumin, ascorbic acid and α-tocopherol. Theoretically, one should be able to reverse these effects through dietary supplementation, especially of vitamin C and E.