The presence of free radicals in biological material has been discovered some 50 years ago. In physiological conditions, free radicals, in the first place the ones of oxygen and nitrogen, are continuously synthesized and involved in the regulation of a series of physiological processes. The excess of free radicals is efficiently eliminated from the body in order to prevent their toxic effects. Toxic effects of free radicals may be classified into three groups: a) change of intracellular redox potential, b) oxidative modification of lipids, proteins and DNA, and c) gene activation. Lipid peroxidation involving cell membranes, lipoproteins and other molecules leads to the production of primary high-reactive intermediaries (alkyl radicals, conjugated dienes, peroxy- and alkoxyl radicals and lipid hydroperoxide), whose further breakdown generates the secondary products of lipid peroxidation: short-chain evaporable hydrocarbons, aldehydes and final products of lipid peroxidation: isoprostanes, MDA, 4-hydroxy-2, 3-transnonenal and 4,5-dihydroxydecenal which are important mediators of atherosclerosis, coronary disease, acute myocardial infarction, rheumatoid arthritis, systemic sclerosis and lupus erythematodes. Oxidative modification of proteins is manifested by changes in their primary, secondary and tertiary structures. Proteins have a specific biological function, and therefore their modification results in unique functional consequences. The nature of protein modification may provide valid information on the type of oxidants causing the damage. Chlorotyrosyl is a specific marker of oxidative damage to tyrosine caused by HOCl action, which most commonly reflects the involvement of neutrophils and monocytes in oxidative stress, while nitrotyrosyl indicates the presence of higher peroxy-nitrite synthesis. Methyonin and cysteine are the amino acids most sensitive to oxidative stress, carbonyl groups are markers of severe damage caused by free radicals, and di-tyrosyl is the most significant and sensitive marker of oxidative modification made by γ rays. >Carbonyl stress< is an important form of the secondary oxidation of proteins, where reducing sugars non-enzymatically react with amino groups of proteins and lipids and give rise to the production of covalent compounds known as advanced glycosylated end products (AGE-products). A hydroxyl radical damages the DNA, leading to a loss of base and the formation of abasic sites (AP sites), break of DNA chain and sugar modification. Final lipid peroxidation products (MDA) may covalently bind to DNA, producing the >DNA radicals< which are responsible for mutations. Measurement of an adequate oxidative stress biomarker may not only point to an early onset of disease, its progression and assessment of therapy effectiveness, but can also help in the clarification of the pathophysiological mechanisms of tissue damage caused by oxidative stress, prediction of disease prognosis and choice of appropriate treatment in the early stages of disease.
The effect of Hyperglycemia and Oxidative Stress on the Development and Progress of Vascular Complications in Type 2 Diabetes
Oxidative stress is the result of increased production of free radicals, which impair the cell function and cause many pathological conditions and diseases. The development of diabetes, its course and complications are closely associated with an imbalance in pro-antioxidative cell state and change of redox potential. Prolonged exposure to hyperglycemia is currently considered the major factor of the pathogenesis of atherosclerosis in diabetes. Atherosclerosis is the cause of about 80% of mortality in diabetics, and over 75% of all hospitalized diabetic patients have associated cardiovascular complications. Hyperglycemia induces different vascular tissue damage at the cellular level, which potentially accelerates the atherosclerotic processes. The most significant mechanisms responsible for acceleration of atherosclerotic processes in diabetic patients are: a) non-enzymatic protein and lipid glycosylation which interferes with normal function, in the way that it deranges molecular conformation, impairs enzymatic function, reduces the capacity of breakdown and interferes with recognition of protein structures by receptors; b) interaction of glycosylated proteins with their receptors resulting in induction of oxidative stress and pro-inflammatory reactions; c) polyol pathway; d) hexosamine pathway and e) activation of protein kinase C and impaired growth factor expression.
Emina Čolak, Vesna Dimitrijević-Srećković, Predrag Đorđević, Sanja Stanković, Nada Majkić-Singh, Katarina Lalić and Nebojša Lalić
The Influence of Type And Duration of Cardiovascular Complications On Antioxidative Parameter Values In Type 2 Diabetic Patients
It is well established that type 2 diabetes mellitus is associated with highly increased risk of coronary heart disease, cardiovascular disease (CVD), and total mortality. CVD is the leading cause of death of people with diabetes. The aim of our study was to test the effect of type and duration of cardiovascular complications on antioxidant parameter values: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status in patients with type 2 diabetes mellitus and manifested cardiovascular complications. Out of 100 subjects included in the study, 69 subjects were type 2 diabetic patients with cardiovascular complications and 31 age-matched controls. Statistical data processing revealed significantly lower antioxidant defense (p<0.001) in patients with type 2 diabetes and cardiovascular complications manifested as coronary artery disease (CAD), hypertension (HTA) and myocardial infarction experienced in the previous 8 years (AMI). The type 2 diabetics with longer history of diabetes and coronary artery disease had higher fasting glucose values, higher GR activity, but lower TAS and SOD activity (p<0.05). Fasting glucose levels were in negative correlation with SOD and GPx activities in the subgroups of diabetics with severe cardiovascular complications (CAD+AMI, CAD+AMI+ HTA) (p<0.05).
Background: Cardiovascular disease (CVD) is a major cause of mortality and morbidity in many populations, especially in developed countries. The aim of the study was to analyze the lipid status in a student population at increased risk for CVD in comparison with students who are not at increased risk for CVD.
Methods: This study included 238 students from the University of Novi Sad of both sexes (126 men and 112 women), with a mean age of 22.32±1.85 years. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) of less and more than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). Total cholesterol - TCH, triglycerides - TG, high density lipoprotein cholesterol - HDL-c, low density lipoprotein cholesterol - LDL-c, very low-density lipoprotein cholesterol - VLDL-c concentrations were determined and the index of atherosclerosis (IA), established risk factors RF-TCH/HDL-c ratio and non-HDL-c/HDL-c ratio were mathematically calculated.
Results: The values of TCH, LDL-c, non-HDL-c, VLDL-c and TG were significantly higher in Group 1 compared to Group 2 (P<0.001). IA, non-HDL-c/HDL-c and RF-TCH/HDL-c ratio were also significantly higher (P<0.001), while HDL-c was significantly lower (p<0.01) in Group 1 compared to controls. These results were not influenced by gender in both groups of subjects.
Conclusions: The data suggest that increased anthropometric parameters are followed by increased lipoprotein status in the group of students at increased risk for CVD and screening of the lipid status is necessary in students, especially in those who are at increased risk for CVD.
Emina Čolak, Dragana Pap, Ljubinka Nikolić and Sanja Vicković
The goal of this study was to assess the oxidative stress status through the values of antioxidant defense parameters: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS), as well as cardiovascular risk factors (total cholesterol, LDL-cholesterol, VLDL-cholesterol, non-HDL-cholesterol and triglycerides), anthropometric parameters (Body mass index-BMI, waist circumference-WC, hipp circumferemce-HC, waist-to-hipp ratio-WHR and inflammatory markers (high sensitive C-reactive protein) in a group of obese adolescents.
A total of 238 students of both sexes, age of 22.32 ± 1.85 yr. were included in the study. According to the values of BMI lower and higher than 25 kg/m2 and WC higher and lower than 94 cm (males)/80 cm (females) the tested group of students was divided into 2 subgroups: Group 1 (increased risk for CVD) and Group 2 (lower risk for CVD).
Significantly reduced SOD and GPx with increased GR, TAS, inflammatory and lipoprotein parameters were obtained in Group 1 compared to Group 2. Significant positive association of hsCRP (OR:1.41; 95%CI 1.08–1.83; P=0.007), TAS (OR:827.2; 95%CI 19.27–35498; P=0.007) and GR (OR:1.13; 95%CI 1.05–1.21; P=0.002) and negative association of GPx (OR:0.97; 95%CI 0.94–1.003; P=0.043) and HDL-cholesterol (OR:0.41; 95%CI 0.176– 0.963; P=0.0014) with cardiovascular risk factors were found in obese students. According to the ROC analysis GR>44.8 U/L, TAS>1.35 mmol/L, hsCRP>1.71 mg/L and HDL-cholesterol <1.13 mmol/L have sufficient predictive ability for cardiovascular disease in obese students.
Significant association of antioxidant defense parameters with anthropometric, lipid and inflammatory markers in obese students with increased cardiovascular risk suggest that screening of these parameters is necessary and highly recommended.
Emina Čolak, Dragana Pap, Nada Majkić-Singh and Ivana Obradović
Background: It has been reported that obesity is associated with metabolic syndrome, insulin resistance, cardiovascular risk but also with nonalcoholic fatty liver disease (NAFLD). The prevalence of obesity in children and adolescents is increasing rapidly all over the world. The aim of this study was to analyze the value of liver enzymes: AST, ALT and γGT in a group of obese students in order to establish their correlation to anthropometric parameters such as: BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist-to-hip ratio) compared to non-obese students who comprised the control group (CG).
Methods: In this study, 238 students from the University of Novi Sad of both sexes (126 men and 112 women) with a mean age of 22.32 ± 1.85 years were included. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) lower and higher than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the obese group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). AST, ALT and γGT activities were determined in fasting blood samples.
Results: Statistical processing data revealed significantly higher values of AST, ALT and γGT in the group of students with BMI>25 kg/m2, WC>94 cm for males and WC>80 cm for females, HC>108 cm for males and HC>111 cm for females, and WHR>0.90 for males and WHR>0.80 for females (P<0.001). Significant association was established between anthropometric parameters and liver enzyme levels (P<0.0001).
Conclusions: Obese students with higher BMI, WC, HC and WHR values have higher liver enzyme activites and a higher chance to develop NAFLD in the future.