Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria.
ABSTRACT High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria.
Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects.
MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P < 0.0001, P < 0.0001; GSH: P < 0.0001, P < 0.0001; GPx: P < 0.0001, P < 0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria (P < 0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria (P < 0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients (P > 0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria (P < 0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients (r = 0.549, P < 0.0001; r = -0.385, P<0.01).
Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.
Article: HUVECs from newborns with a strong family history of diabetes show diminished ROS synthesis in the presence of high glucose concentrations.[show abstract] [hide abstract]
ABSTRACT: A family history of type 2 diabetes mellitus (DM) increases the probability to develop DM and endothelial dysfunction. The probable mechanism involves augmented reactive oxygen species (ROS) synthesis. The aim of this study was to evaluate the synthesis of ROS in human umbilical vein endothelial cells (HUVECs) obtained from healthy newborns with (experimental) and without (control) a strong family history of type 2 DM, exposed to different glucose concentrations. HUVECs were exposed to various glucose concentrations for 24 and 48 h periods, before cell proliferation, mitochondrial activity, and mitochondrial membrane potential were determined. Intracellular ROS synthesis in the presence or absence of the mitochondrial uncoupler CCCP, cytochalasin B, or diphenyleneiodonium (DPI) was also evaluated. As opposed to control HUVECs, we found that experimental HUVECs exposed to 30 mmol/L glucose showed a 50% decrease in cell proliferation, a 90% reduction in mitochondrial activity, and a statistically significant inhibition of ROS synthesis in the presence of CCCP or cytochalasin B; DPI had no effect. Our results suggest that mitochondria and NAD(P)H-oxidase from HUVECs obtained from healthy newborns with a family history of DM have an innate deficient response to high glucose concentrations.Diabetes/Metabolism Research and Reviews 02/2007; 23(1):71-80. · 3.37 Impact Factor
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ABSTRACT: The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans. To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of N(G)-monomethyl-L-arginine (L-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function. There was a significant increase in the UACR in response to NOS inhibition with L-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to L-NMMA was not related to the increase in the UACR in response to L-NMMA in either population, even after adjusting for filtration fraction. NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria.Diabetes 02/2011; 60(2):572-6. · 8.29 Impact Factor
Article: Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages.[show abstract] [hide abstract]
ABSTRACT: Diabetes is associated with increased oxidative stress and atherosclerosis development. In the present study, we investigated the effects of pomegranate juice (PJ; which contains sugars and potent anti-oxidants) consumption by diabetic patients on blood diabetic parameters, and on oxidative stress in their serum and macrophages. Ten healthy subjects (controls) and 10 non-insulin dependent diabetes mellitus (NIDDM) patients who consumed PJ (50ml per day for 3 months) participated in the study. In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances (TBARS) were both increased, by 350% and 51%, respectively, whereas serum SH groups content and paraoxonase 1 (PON1) activity, were both decreased (by 23%). PJ consumption did not affect serum glucose, cholesterol and triglyceride levels, but it resulted in a significant reduction in serum lipid peroxides and TBARS levels by 56% and 28%, whereas serum SH groups and PON1 activity significantly increased by 12% and 24%, respectively. In the patients versus controls monocytes-derived macrophages (HMDM), we observed increased level of cellular peroxides (by 36%), and decreased glutathione content (by 64%). PJ consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%) in the patients' HMDM. The patients' versus control HMDM took up oxidized LDL (Ox-LDL) at enhanced rate (by 37%) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake (by 39%). We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in anti-oxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.Atherosclerosis 09/2006; 187(2):363-71. · 3.79 Impact Factor