Oxidative stress versus antioxidant defenses in patients with acute myocardial infarction

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with increasing production of reactive oxygen species (ROS). The imbalance between ROS production and antioxidant defenses leads to the condition known as oxidative stress. The most widely recognized effect of increasing oxidative stress is the oxidation and damage of macromolecules, membranes, proteins, and DNA. Therefore, in this study we sought to evaluate oxidative stress and antioxidant defenses in patients with AMI. Lipid peroxidation, protein carbonyl levels, and enzymatic and nonenzymatic antioxidants were assessed in samples obtained from 40 AMI patients and 40 control patients. AMI was characterized by clinical, electrocardiographic, and laboratory criteria. The control group was divided into two groups of 20 patients: a control group with healthy patients and a risk group. Our results demonstrated an increase in substances reactive to thiobarbituric acid (TBARS) and carbonyl protein levels in the AMI and risk groups. In addition, a positive correlation was found between TBARS, carbonyl protein levels, and troponin I in AMI patients. Surprisingly, for the enzymatic antioxidant defenses, catalase and superoxide dismutase, we observed an increase in these parameters in the AMI and risk groups when compared with healthy patients. However, a decrease in nonenzymatic antioxidants such as vitamin C and vitamin E was observed in AMI patients when compared with the healthy group and the risk group. The increase in oxidative stress was probably a result of the elevation in ROS production due to the ischemic/reperfusion event that occurs in AMI, in addition to the decrease of nonenzymatic antioxidant defenses.     

氧化损伤标志物与中枢神经系统疾病

中枢神经系统疾病中自由基的增加引发氧化应激,从而导致中枢神经系统损伤,故氧化损伤标志物的检测对疾病的早期诊断、病情评价及预后均具有重要意义。本文主要介绍氧化损伤中脂质、蛋白质、DNA的氧化生物标志物以及相关酶和非酶抗氧化剂的间接标志物。过去10年,虽然报道了中枢神经系统疾病的一些氧化应激标志物,但仍需寻找同时具备敏感度高和专一性强的氧化损伤标志物。     

Effect of haemodialysis on the oxidative stress and antioxidants in diabetes mellitus

Abstract Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species (ROS) production and antioxidant systems. It is involved in the pathogenesis of different chronic diseases. High levels of ROS production via different biochemical mechanisms accompany diseases like type 2 diabetes mellitus (DM) and end-stage renal disease (ESRD). Elevated oxidative status and reduced antioxidant defence systems in patients with DM and ESRD accelerate the prevalence of atherosclerosis and other chronic complications. Our aim was to reveal the effects of diabetes and haemodialysis (HD) separately and together on oxidative stress. In our study, we included 20 diabetic (DM) patients with no renal disease, 20 non-diabetic haemodialysis (HD), 20 diabetic haemodialysis (DHD) patients and 20 healthy volunteers. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances (TBARS), oxidative protein damage as indicated by protein carbonyl (PCO) content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) in all patient groups and healthy subjects. We found enhanced oxidative stress in all patient groups due to an increase in lipid peroxidation (TBARS) and increased oxidative protein damage in terms of PCO content and reduced activities of SOD, CAT and GSH-Px. Oxidative stress was more profound in diabetic patients undergoing haemodialysis. We conclude that both diabetes and dialysis increase oxidative stress and their combined effect on oxidative stress is the highest in magnitude as observed in diabetic patients undergoing haemodialysis.     

Decrease in mitochondrial oxidative protein damage parameters in the streptozotocin-diabetic rat

BACKGROUND: Many authors have shown that hyperglycemia leads to an increase in oxidative protein damage in diabetes. The aim of this study was to reveal the susceptibility of mitochondria from liver, pancreas, kidney, and skeletal muscle of diabetic Sprague-Dawley rats, a model of type 1 diabetes, to oxidative protein damage. METHODS: Mitochondrial fractions were obtained by differential centrifugation. To show the effect of hyperglycemia in promoting oxidative protein damage, we determined mitochondrial protein carbonyl, total thiol, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels. The levels of the studied markers, except nitrotyrosine, were determined by colorimetric methods. Nitrotyrosine levels were measured by ELISA. All values were compared with those of the controls by using the Mann-Whitney U-test. RESULTS: Nitrotyrosine and lipid hydroperoxide levels were decreased and other parameters were not changed in liver mitochondria of diabetic rats. Protein carbonyl, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels were decreased and total thiol levels were not changed in pancreas mitochondria of diabetic rats. Only advanced oxidation protein products and lipid hydroperoxide levels were decreased in kidney mitochondria of diabetic rats. The levels of the same parameters were not significantly different in muscle mitochondria of diabetic rats. CONCLUSIONS: The decrease in mitochondrial oxidative protein damage in diabetes may correspond to either an increase in antioxidant defense mechanisms or a different adaptive response of the cells to the increased extramitochondrial oxidative stress in diabetes. The mitochondrial oxidative protein damage-lowering mechanisms in diabetes remain to be clarified.     

Lipid peroxidation,antioxidants, lipid profile,and HbA1c in diabetic patients

Diabetes mellitus is characterized by hyperglycemia together with biochemical changes in glucose, lipid profile, lipid peroxidation, and antioxidants status. This study aims to assess lipid profile, lipid peroxidation, antioxidants, and glycated hemoglobin (HbA1c) in type 1 and type 2 diabetic subjects. Type 1 and type 2 diabetic patients were selected from the subjects attending OPD in Nepalgunj Medical College, Nepal, for medical checkup. Fasting blood sugar (FBS), lipid profile, lipid peroxidation (malondialdehyde), and antioxidants status (reduced glutathione and vitamin E) were estimated in both groups and were compared with healthy controls. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was calculated to assess the cardiovascular risk factors. When type 1 diabetic patients were compared with type 2 diabetic patients, it showed statistically significant increase in the levels of HbA1c, triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C), whereas statistically significant decreased level was found in malondialdehyde (MDA). FBS, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), vitamin E, and HDL/LDL ratio were not significant. Early diagnosis of dyslipidemia and oxidative stress can be used as a preventive measure for the development of microvascular and macrovascular complications in type 1 and type 2 diabetes mellitus.     

Susceptibility of erythrocytes from non-insulin-dependent diabetes mellitus and hemodialysis patients, cigarette smokers and normal subjects to in vitro oxidative stress and loss of deformability

Incubation of normal erythrocytes with 10 mM H2O2 has caused a loss of deformability. This loss of deformability was correlated with the extent of malonyldialdehyde, MDA (an indicator of lipid peroxidation) and alanine production (an indicator of protein degradation). The susceptibility of erythrocytes from 21 non-insulin-dependent diabetes mellitus (NIDDM) and 18 hemodialysis patients, 21 cigarette smokers and 25 healthy controls to in vitro oxidative stress with H2O2 has been measured as MDA production. Besides this, their erythrocytes reduced glutathione (GSH; an antioxidant) level has also been determined, but before exposure to H2O2. Erythrocytes from NIDDM and hemodialysis patients have shown significant increase in MDA production and a significantly low GSH level, compared to healthy controls. In cigarette smokers, although the GSH level was significantly low, but there was no significant difference in MDA production, compared to healthy controls. The low GSH level in NIDDM and hemodialysis patients, and smokers indicates that their erythrocytes were exposed to oxidative stress (an increase in free radical load) in vivo, resulting in an overconsumption and/or decreased production of GSH. The increased susceptibility to oxidative stress along with the decrease in some antioxidants (e.g., GSH) may explain the significant increase in MDA production in NIDDM and hemodialysis patients. But in cigarette smokers, the increased susceptibility to oxidative stress is probably not sufficient to cause a significant increase in MDA production. The results may also indicate an increased susceptibility to the loss of erythrocyte deformability in NIDDM and hemodialysis patients compared to healthy controls.     

Effect of aminoguanidine on lipid peroxidation in streptozotocin-induced diabetic rats.

Diabetes mellitus is postulated to be associated with increased lipid peroxidation, which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine (AMGN), the prototype inhibitor of advanced glycosylation end product (AGE) formation, has been recently shown to prevent oxidative modification of low-density lipoprotein (LDL) in vitro at a moderate concentration. It is unknown whether AMGN may act as an antioxidant against lipid peroxidation under hyperglycemia in vivo. To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN (1 g/L in drinking water) or vitamin E (400 mg/d for 5 d/wk) to streptozotocin (STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II (FOX method) and red blood cell (RBC) membrane malondialdehyde (MDA) and related aldehydes as thiobarbituric acid-reactive substances (TBARS). Plasma lipid hydroperoxide was higher in STZ-induced diabetic rats versus control rats (mean +/- SD, 7.53 +/- 2.03 v 5.62 +/- 0.44 micromol/L, P < .05; n = 8 to 14). RBC membrane TBARS were also higher in STZ-induced diabetic rats than in control rats (2.67 +/- 0.46 v 1.81 +/- 0.19 nmol/mL, P < .05). Plasma lipid hydroperoxide was lower in AMGN-treated (6.23 +/- 0.59 micromol/L, P < .05) and vitamin E-treated (5.29 +/- 0.27 micromol/L, P < .05) diabetic rats than in untreated diabetic rats. RBC membrane TBARS were also lower in AMGN-treated (1.93 +/- 0.12 nmol/mL, P < .05) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, cholesterol, and triglyceride levels among diabetic groups. Although the mechanism(s) of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN may have an additional beneficial effect as an antioxidant against lipid peroxidation in a prevention trial for diabetic vascular complications.     

Influence of mulberry (Morus indica L.) leaves on antioxidants and antioxidant enzymes in STZ-diabetic rats

To assess the influence of mulberry (Morus indica L.) leaves on antioxidants and antioxidant enzymes in STZ- diabetic rats as the leaves of mulberry (Morus indica L.) of Moraceae, are reported to be rich in a no. of bioactive principles i.e. antioxidant vitamins, flavonoids and moracins that can fight against oxidative stress in diabetes. STZ-diabetic rats were treated with dried mulberry leaves incorporated in the feed at 25 % level (as per dose response) for 8 weeks in standard experimental conditions in comparison with diabetic glibenclamide–treated and diabetic control rats. At the end of experimental period, fasting blood glucose, serum non-enzymatic antioxidants, hepatic lipid peroxidation and antioxidant enzymes were assayed in all the experimental groups. Hyperglycemia, a 274 % (P?<?0.01) rise in fasting blood glucose and increased oxidative stress as shown by a two fold increase in lipid peroxidation in hepatic tissue, decreased serum non enzymatic antioxidants viz. vit.C (51 %) and E (47 %), significantly decreased activities of hepatic antioxidant enzymes such as glucose-6-phosphate dehydrogenase (43 %), glutathione peroxidase (41 %) and superoxide dismutase (44 %) and significantly increased activity of catalase (39 %) in STZ-diabetic rats were ameliorated by mulberry leaves which is evidenced by significant fall in fasting glucose, and lipid peroxidation, rise in antioxidants as well as the activities of defense enzymes and decrease in the activity of catalase while the antidiabetic drug, glibenclamide showed lesser effects than mulberry leaves. Mulberry leaves protected STZ-diabetic rats against oxidative stress by improving antioxidants and the activities of defense enzymes and controlling hyperglycemia and lipid peroxidation in a better way than the drug.     

Nerve conduction and antioxidant levels in experimentally diabetic rats: effects of streptozotocin dose and diabetes duration

Oxidative stress supposedly plays a role in the pathogenesis of diabetic neuropathy. We have studied whether a variation in the streptozotocin (STZ) dose or diabetes duration affects the outcome of measurements of oxidative damage in relation to nerve conduction. In experiment 1, we induced diabetes in rats using 40 or 60 mg/kg STZ intravenously and assessed sciatic nerve conduction velocity. After 18 weeks, we measured plasma malondialdehyde (MDA) and red blood cell (RBC) and nerve glutathione levels. We observed a dose-dependent effect of STZ on body weight, and to a lesser extent on nerve conduction, but not on RBC or nerve glutathione and plasma MDA. In experiment 2, we administered a fixed dose of STZ (40 mg/kg) and measured antioxidants and MDA in RBCs, plasma, and sciatic nerve after 2, 4, 8, and 18 weeks in diabetic and control rats. RBC glutathione decreased in diabetic animals initially, but did not differ from control values after week 4. Plasma total glutathione increased until week 8. The ratio of total to oxidized glutathione in the sciatic nerve from diabetic animals paralleled the decrease observed in RBCs, and subsequently increased compared with controls. Nerve catalase increased in diabetic animals. Endoneurial MDA remained unchanged, whereas plasma MDA increased and RBC superoxide dismutase (SOD) decreased in the diabetic group. We conclude that differences in antioxidant levels between STZ-diabetic and control rats depend on the duration of hyperglycemia. Furthermore, dose-related effects of STZ on nerve conduction are not reflected in endoneurial lipid peroxidation or glutathione.     

Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats

This study was performed to determine whether or not hyperglycemia in diabetes results in elevated levels of lipid peroxidation products in red blood cells (RBC). Diabetes was induced in rats by treatment with streptozotocin. The level of lipid peroxidation products was examined in fresh RBC by measuring their thiobarbituric acid (TBA) reactivity after 2 and 4 months of induction of diabetes. Hyperglycemia was assessed by measuring the level of glycosylated hemoglobin and blood glucose. Results show that lipid peroxidation levels were significantly higher (50% to 84%) in RBC of diabetic rats than in controls. The increase in the level of lipid peroxidation was blocked in diabetic rats in which hyperglycemia was controlled by insulin treatment. Among phospholipid classes, relative percentage of sphingomyelin (SM) was significantly reduced in RBC at both 2 and 4 months of diabetes; whereas phosphatidylethanolamine (PE) levels were higher in RBC at 4 months of diabetes only. The level of phosphatidylcholine (PC) did not differ significantly between RBC of control and diabetic rats. This study suggests a significantly altered lipid composition and an accumulation of lipid peroxidation products in RBC of streptozotocin-treated diabetic rats.     

Effect of vitamin E on oxidative stress status in small intestine of diabetic rat

AIM:To investigate the effect of vitamin E on oxidative stress status in the small intestine of diabetic rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups:Control (C),non-treated diabetic (NTD) and vitamin E-treated diabetic (VETD) groups. The increases in lipid peroxidation,protein oxidation and superoxide dismutase (SOD) in these three groups was compared after 6 wk. RESULTS:There was no significant difference in catalase activity between NTD and control rats. Compared to NTD rats,the treatment with vitamin E significantly decreased lipid peroxidation and protein oxidation,and also increased catalase activity and SOD. CONCLUSION:The results revealed the occurrence of oxidative stress in the small intestine of diabetic rats. Vitamin E,as an antioxidant,attenuates lipid peroxidation and protein oxidation,and increases antioxidant defense mechanism.     

Oxidative stress in Cohen diabetic rat model by high-sucrose, low-copper diet: inducing pancreatic damage and diabetes

Increased oxidative stress contributes to the development and progression of both types of diabetes mellitus (DM) and its complications. In the Cohen diabetic (CD) rats, a known genetic model of nutritionally induced type 2 DM, a high-sucrose, low-copper diet (HSD) induces within 4 weeks DM in the sensitive (CDs) rats but not in the resistant (CDr) rats. To assess the possible involvement of oxidative stress in the induction of DM, we studied the effect of HSD on the tissue levels of antioxidants and the extent of oxidative injuries in these animals in comparison with the regular outbred strain of nondiabetic Sabra rats. The specific aims were to investigate, at the onset of HSD-induced DM, (1) the extent of oxidative injury, as reflected by levels of malondialdehyde and protein carbonyl groups; (2) the overall antioxidant capacities to cope with increased oxidative stress; and (3) the modification of oxidative damage biomarkers in various tissues of CDr, CDs, and Sabra rats. Female CDs, CDr, and Sabra rats were fed regular diet or HSD for 4 to 5 weeks; and several parameters of oxidative injuries and antioxidant levels were determined. Changes in the levels of nonenzymatic low-molecular weight antioxidants (LMWAs) were measured by cyclic voltammetry and oxygen radical absorbance capacity. The activities of the antioxidant enzymes superoxide dismutase and catalase were measured. Oxidative damage was evaluated by measuring lipid peroxidation and protein oxidation. (1) In all animals fed HSD, the levels of LMWAs were decreased in most organs, although not plasma. (2) A significant difference was consistently found in antioxidant enzymes' activities in the pancreas of HSD-fed CDs rats, but not in other tissues. (3) The activities of superoxide dismutase and catalase and the levels of malondialdehyde and protein carbonyl group increased, whereas the levels of LMWAs decreased, in the pancreas of HSD-fed CDs rats. In the CD rats that develop DM when fed HSD, the pancreas showed susceptibility to oxidative stress-induced injuries. Thus, enhanced oxidative stress seems to play a role in the pathogenesis of DM in this strain.     

Blood antioxidant defense system and dietary survey of elderly diabetic men

Levels of antioxidants, activities of free radical scavenging enzymes and extent of lipid peroxidation were determined in the blood of 37 elderly diabetic men and 30 control elderly men, 16 without cardiovascular disease (CVD) and 14 with CVD. The mean +/-S.D. of the ages of the diabetic men was 66+/-5 and those of the control men was 69+/-5, while serum glucose levels of diabetic men were 213+/-81 mg/dl and that of control subjects were 95+/-14 mg/dl. Among the diabetic men, 13 men were obese with body mass index>30, 26 men had poor control of diabetes (glycohemoglobin>7%) and 25 men had retinopathy. The diets of the control and diabetic men were evaluated. Blood samples were collected and analyzed for major endogenous antioxidant defense parameters and lipid peroxidation. The results show that diabetic men had significantly lower blood reduced glutathione levels (p<0.001) and erythrocyte (RBC) CuZn-superoxide dismutase activity (p<0.001) when compared to control groups with or without CVD. There was no significant differences in plasma vitamin E levels and the activities of catalase and glutathione peroxidase in RBC among the three groups. The extent of lipid peroxidation was highest in diabetic patients, intermediate in controls with CVD, and lowest in controls without CVD. The results suggest that a decline of endogenous antioxidant defense capability contributes to oxidative stress in the diabetic elderly patients. Dietary survey showed that there were no differences in the nutrient intakes of diabetic and control groups. It appears that individual dietary advice is needed for a large portion of diabetic patients in view of their poor glycemic control, hypertriglyceridemia and obesity.     

Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia

Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease.     

The susceptibility of red blood cells to autoxidation in type 2 diabetic patients with angiopathy

We examined the in vitro susceptibility of red blood cell (RBC) lipids to oxidation in type 2 diabetic patients with or without angiopathy. Lipid peroxidation was assessed by quantifying thiobarbituric acid (TBA) reactivity as malondialdehyde (MDA). We also examined the RBC antioxidant status by determining glutathione (GSH) levels. Before in vitro oxidation, RBC MDA levels were significantly higher in both diabetic groups than in the controls (P < .001), and a significant difference was found between the two diabetic groups (P < .05). After in vitro treatment of RBCs with hydrogen peroxide, the degree of lipid peroxidative damage was significantly higher in diabetic patients with angiopathy versus diabetics without angiopathy (P < .001). Diabetic patients have low RBC GSH levels compared with controls, and after in vitro oxidation, the levels were significantly decreased in diabetics (P < .001). There was not a significant correlation between RBC MDA levels and glycated hemoglobin (GHb), plasma cholesterol, and triglyceride. The correlation between RBC MDA and GSH was weak (P < .001). We suggest that the results of this study might help to clarify the role of oxidative mechanisms as an in vitro model of degenerative damage in type 2 diabetic angiopathic complications.     

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism

Background  Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS.
Subjects and methods  Serum TAS, MDA, C-reactive protein levels and lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and 40 healthy subjects.
Results  MDA was elevated in both hypothyroid and subclinical hypothyroid patients compared with controls, while TAS levels show no significant differences between groups. Low-density lipoprotein (LDL) cholesterol levels were significantly high in both hypothyroid and subclinical hypothyroid patients. Triglyceride levels were high only in hypothyroid patients when compared with the controls. MDA showed a correlation with LDL cholesterol, total cholesterol and triglyceride.
Conclusions  These results suggest an increased oxidative stress in both hypothyroid and subclinical hypothyroidism states, which can be explained by both the insufficient increase in the antioxidant status and the altered lipid metabolism in these cases.     

Glycated hemoglobin and lipid peroxidation in erythrocytes of diabetic patients

In diabetes, glycation and subsequent browning (or glycoxidation) reactions are enhanced by elevated glucose concentrations. It is unclear whether the diabetic state per se also induces an increase in the generation of oxygen-derived free radicals (OFRs). However, there is some evidence that glycation itself may induce the formation of OFRs. OFRs cause oxidative damage to endogenous molecules, including cholesterol. 7-Oxocholesterol is known to be one of the major products of cholesterol oxidation. The level of cholesterol peroxidation products was assessed in erythrocyte membrane lipid by monitoring the peak height ratio of 7-oxocholesterol, one of the products of cholesterol peroxidation, to cholesterol with gas chromatography/mass spectrometry (GC/MS). The peak height ratio of 7-oxocholesterol to cholesterol was used as a biomarker of lipid peroxidation. The hemoglobin A1c (HbA1c) value, an index of glycemic stress, was measured by high-performance liquid chromatography. We examined the relationship between the levels of cholesterol peroxidation products and HbA1c in erythrocytes of diabetic and healthy subjects. There was a significantly increased ratio of 7-oxocholesterol to cholesterol in diabetic erythrocytes compared with control erythrocytes. The ratio of 7-oxocholesterol to cholesterol was significantly correlated with the level of HbA1c. This suggests that glycation of hemoglobin via chronic hyperglycemia is linked to cholesterol peroxidation in erythrocytes of both diabetic and healthy subjects.     

Susceptibility of low- and high-density lipoproteins from diabetic subjects to in vitro oxidative modification.

AIMS: To investigate the hypothesis that lipid peroxidation of both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) is important in the development of atherosclerosis. METHODS: We have investigated whether LDL and HDL from patients with Type 1 diabetes mellitus (DM, n = 16) and Type 2 DM (n = 15) is more susceptible to Cu2+ -induced lipid peroxidation than LDL and HDL from a similar number of nondiabetic controls matched for age, gender and serum cholesterol. RESULTS: The vitamin E content of LDL and HDL from both groups of diabetic patients was not significantly different from controls. The LDL from Type 2 diabetic patients and HDL from both diabetic groups were significantly richer in triglyceride than controls. Phospholipid was decreased in LDL from Type 2 diabetic patients and protein was decreased in HDL in Type 1 DM, but otherwise the composition of LDL and HDL in diabetic subjects was similar to controls. No significant differences were observed in the generation of conjugated dienes or lipid peroxides in either LDL or HDL when the two groups were compared with each other or with their respective controls. CONCLUSIONS: Increased lipid peroxidation occurring in vivo in diabetes is unlikely to be the result of increased susceptibility of lipoproteins to lipid peroxidation, but rather to increased generation of free radicals, to oxidation of lipids other than those present in serum lipoproteins or to decreases in antioxidant systems other than the fat-soluble antioxidants present in lipoproteins.     

Protein oxidation in Type 2 diabetic patients on hemodialysis

BACKGROUND: Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy. There have been many reports on increased production of oxidants and decreased level of antioxidants in diabetic patients. The dialysis procedure contributes to oxidative stress. An increase in oxidative stress may contribute to the development of oxidative protein damage in diabetic patients. Our aim was to reveal the effects of diabetes and hemodialysis (HD) on oxidative modifications of plasma proteins. METHODS: We measured reactive carbonyl derivates (PCO), protein thiol (P-SH), and reduced glutathione (GSH) levels in Type 2 diabetic (DM) and diabetic hemodialysed patients (DHD) and in healthy control participants. RESULTS: Protein carbonyl (PCO) content increased significantly in all patient groups relative to the controls. The dialysis procedure caused an additional increase in PCO levels in DHD patients before and after dialysis compared with the level in DM patients. There was a significant decrease in P-SH levels in DHD patients compared with the level in healthy participants and DM patients. There was no significant difference in the whole blood GSH levels between the DM patients and control participants. It was significantly higher in DHD patients in comparison to the DM patients. CONCLUSIONS: We conclude that PCO level increases in DM patients, and this increase is more profound in DHD patients, indicating that both diabetes and dialysis contribute to increased protein oxidation. The low P-SH level in DHD patients, but not in DM patients, suggests that dialysis is responsible for this decrease. We propose plasma PCO derivate as a novel specific marker for oxidative protein damage.     

High-Dose Testosterone Propionate Treatment Reverses the Effects of Endurance Training on Myocardial Antioxidant Defenses in Adolescent Male Rats

This study was aimed at evaluation of changes in activities of selected antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and contents of key nonenzymatic antioxidants (glutathione, protein thiol groups, and α- and γ-tocopherols) in the left heart ventricle of young male Wistar rats subjected to endurance training (treadmill running, 1 h daily, 5 days a week, for 6 weeks) or/and testosterone propionate treatment (8 or 80 mg/kg body weight, intramuscularly, once a week, for 6 weeks) during adolescence. The training alone increased the activities of key antioxidant enzymes, but lowered the pool of nonenzymatic antioxidants and enhanced myocardial oxidative stress as evidenced by elevation of the lipid peroxidation biomarker malondialdehyde. The lower-dose testosterone treatment showed mixed effects on the individual components of the antioxidant defense system, but markedly enhanced lipid peroxidation. The higher-dose testosterone treatment decreased the activities of the antioxidant enzymes, lowered the contents of the nonenzymatic antioxidants, except for that of γ-tocopherol, reversed the effect of endurance training on the antioxidant enzymes activities, and enhanced lipid peroxidation more than the lower-dose treatment. These data demonstrate the potential risk to cardiac health from exogenous androgen use, either alone or in combination with endurance training, in adolescents.