Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies.

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates of increases in prevalence. Diabetic nephropathy (DN) is a specific kind of kidney damage that occurs in 40% of patients with DM and is considered a serious complication of DM. Most modern methods for treatments aimed at slowing down the progression of DN have side effects and do not produce unambiguous positive results in the long term. This fact has encouraged researchers to search for additional or alternative treatment methods. Hyperglycemia has a negative effect on renal structures due to a number of factors, including the activation of the polyol and hexosamine glucose metabolism pathways, the activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, the accumulation of advanced glycation end products and increases in the insulin resistance and endothelial dysfunction of tissues. The above mechanisms cause the development of oxidative stress (OS) reactions and mitochondrial dysfunction, which in turn contribute to the development and progression of DN. Modern antioxidant therapies for DN involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), which are widely used not only for the treatment of diabetes but also other systemic diseases. It has also been suggested that therapeutic approaches that target the source of reactive oxygen species in DN may have certain advantages in terms of nephroprotection from OS. This review describes the significance of studies on OS biomarkers in the pathogenesis of DN and analyzes various approaches to reducing the intensity of OS in the prevention and treatment of DN.

Peripheral and regional blood bloodstreams lipid peroxidation comparative analysis in women with pelvic venous disorder.

Pelvic venous disorder (PVD) in women is a polyetiological multifactorial disease characterized by a high prevalence (up to 80%), a high risk of infertility, and a progressive recurrent course. Morphological changes of the venous bed occur in PVD, contributing to retrograde blood flow and pelvic phlebohypertension. It is occur due to dynamic hypervolemia and hypertension long-term exposure on the venous wall. However, PVD pathogenesis analysis only from venous hemodynamic disorders position does not explain all mechanisms of the disease development and does not contribute to the treatment measures effectiveness. Currently oxidative stress reactions are considered as the most important markers of the pathological process. The aim of our work was a comparative analysis of lipid peroxidation-antioxidant defense component changes in the peripheral and regional blood flow in women with primary pelvic venous disorder depending on the disease stage. The study involved 137 women of reproductive age (mean age 37.4±9.1 years old) with diagnosed primary PVD divided into 3 groups according to the pathological process stages (stages I, II, III). Data from 30 practically healthy women (mean age 33.5±6.3 years old) were used as controls. Spectrophotometric, fluorometric, immunoassay and statistical methods were used. In patients with PVD stage I in peripheral bloodstream were higher values of SOD and GPO activity; in the regional bloodstream were higher levels of TBARs, SOD, catalase, GPO and lower GSH. In PVD stage II the peripheral bloodstream showed elevated levels of DC, GSH and SOD reduced levels; the regional bloodstream showed higher levels of DC, TBARs, GPO and GSH reduced levels relative to controls. PVD stage III was characterized by: higher levels of DC and TBARs and lower levels of SOD and GSH in the peripheral bloodstream; higher levels of DC, TBARs and lower levels of GSH and catalase in the regional bloodstream compared with control. Thus, the results of our study showed no significant differences in the LPO-AOD system between peripheral and regional bloodstreams in patients with PVD depending on the disease stage. However, negative changes in the redox balance in the regional bloodstream were earlier and were already registered at the first stage of the disease. It is likely that control of antioxidant insufficiency in patients with PVD should be an important component of preventive measures in the early stages and pathogenetic treatment in the pathological process progression, particularly in stage III of the disease.

Lipid peroxidation functional state changes in patients with obstructive jaundice depending on the level of bilirubin in the blood.

Obstructive jaundice (OJ) is the most common syndrome among diseases of the hepatopancreatoduodenal region and is found in 12-45% of cases. OJ may be benign and malignant etiology. Despite the evidence of the participation of bilirubin in reducing the bactericidal properties of neutrophils, there are no data currently on changes in the functioning of the antioxidant defense system depending on the level of bilirubin in the blood of patients with OJ of various origins. Research in this direction reveals the possibility for the development of pathogenetic recommendations for influencing these links of the pathogenesis of the disease. The study included men with OJ of non-malignant (OJNMG) (n = 47; mean age - 52.02 ± 5.18 years) and OJ of malignant genesis (OJMG) (I-II stages of the malignant process) (n = 45; mean age - 53.02 ± 4.8 years), divided into three subgroups, depending on the level of bilirubin in the blood. The indicators of practically healthy men as a control (n = 50, average age - 48.7 ± 3.9 years) were used. Spectrophotometric and statistical research methods were used. A statistically significant decrease of superoxide dismutase, glutathione-S-transferase, glutathione-peroxidase, ceruloplasmin, an increase in the values of diene conjugates, malondialdehyde in the group of patients with OJNMG relative to the control was revealed, regardless of the level of bilirubin in the blood. The presence of malignant genesis of the disease with more intense changes in the studied parameters relative to control is accompanied. Comparison of indicators between groups of patients with OJ of different genesis showed a decrease in the values of glutathione-S-transferase and an increase in the level of diene conjugates in patients with OJMG and the level of bilirubin less than 60 µmol / L, as well as an increase in the content of diene conjugates in patients with OJNMG and a level of bilirubin 60- 200 µmol / L in comparison with the corresponding groups of patients with OJNMG. Thus, both in the groups with OJNMG and in the groups with OJMG, there is a significant decrease in the activity of the main antioxidant enzymes and an increase in lipid peroxidation products, regardless of the level of bilirubin in the blood. The presence of malignant genesis is characterized by more intense differences. The revealed changes can serve as additional criteria for optimizing the diagnosis and treatment of this cohort of patients.

Lipid peroxidation and antioxidant protection in girls with type 1 diabetes mellitus during reproductive system development.

BACKGROUND AND OBJECTIVE: Type 1 diabetes mellitus (T1D) is found worldwide and is regarded as one of the main risks to human health. The objective of this study was to determine the state of lipid peroxidation (LPO) and antioxidant protection in girls with T1D type considering the stages of reproductive system development. MATERIALS AND METHODS: This study enrolled 56 young girls with T1D and 60 healthy girls (control) matched by age. The study population was divided into 3 age groups: prepubertal, adolescent, and juvenile. The state of LPO and antioxidant system was assessed using the coefficient of oxidative stress that represented the ratio of LPO products to general antioxidative blood activity. Spectrophotometric and fluorometric methods were applied. RESULTS: The results of our study showed increased conjugated diene (CD) and thiobarbituric acid reactant (TBAR) concentrations as well as a decreased reduced glutathione level in prepubertal girls with T1D. Adolescent girls with T1D had a significantly greater CD level and juvenile girls with T1D had a significantly greater TBAR level and lower α-tocopherol concentration than girls in the control group. The greatest coefficient of oxidative stress (1.16) was observed in the prepubertal period. CONCLUSIONS: The prepubertal period is characterized by the most severe state of lipid peroxidation process-antioxidant protection.

Ethnicity and the Prevalence of Polycystic Ovary Syndrome: The Eastern Siberia PCOS Epidemiology and Phenotype Study.

CONTEXT: Previous studies have shown that the prevalence of polycystic ovary syndrome (PCOS) may vary according to race/ethnicity, although few studies have assessed women of different ethnicities who live in similar geographic and socio-economic conditions. OBJECTIVE: To determine the prevalence of PCOS in an unselected multiethnic population of premenopausal women. DESIGN: A multicenter prospective cross-sectional study. SETTINGS: The main regional employers of Irkutsk Region and the Buryat Republic, Russia. PARTICIPANTS: During 2016-19, 1398 premenopausal women underwent a history and physical exam, pelvic ultrasound, and testing during a mandatory annual employment-related health assessment. MAIN OUTCOME MEASURES: PCOS prevalence, overall and by ethnicity in a large medically unbiased population, including Caucasian (White), Mongolic or Asian (Buryat), and mixed ethnicity individuals, living in similar geographic and socio-economic conditions for centuries. RESULTS: PCOS was diagnosed in 165/1134 (14.5%) women who had a complete evaluation for PCOS. Based on the probabilities for PCOS by clinical presentation observed in the cohort of women who had a complete evaluation we also estimated the weight-adjusted prevalence of PCOS in 264 women with an incomplete evaluation: 46.2 or 17.5%. Consequently, the total prevalence of PCOS in the population was 15.1%, higher among Caucasians and women of Mixed ethnicity compared to Asians (16.0% and 21.8% vs. 10.8%, pz <0.05). CONCLUSIONS: We observed a 15.1% prevalence of PCOS in our medically unbiased population of premenopausal women. In this population of Siberian premenopausal women of Caucasian, Asian and Mixed ethnicity living in similar geographic and socio-economic conditions, the prevalence was higher in Caucasian or Mixed than Asian women. These data highlight the need to assess carefully ethnic-dependent differences in the frequency and clinical manifestation of PCOS.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

The Association of Respiratory Viruses with Oxidative Stress and Antioxidants. Implications for the COVID-19 Pandemic.

The spread of a new strain of coronavirus, SARS-CoV-2, a pandemic, poses a serious health problem for all humanity. Compared with the previous outbreaks of coronavirus infection in 2002 and 2012, COVID-19 infection has high rates of lethality, contagiousness, and comorbidity. The effective methods of prevention and treatment are extremely limited. Oxidative stress is actively involved in the mechanisms of initiation and maintenance of violations of homeostatic reactions in respiratory viral infections. It is important to stop systemic inflammation aimed at "extinguishing" the cytokine "storm", caused by the production of reactive oxygen species. Antioxidant defense medications, such as vitamin C, N-acetylcysteine, melatonin, quercetin, glutathione, astaxanthin, polyphenols, fat-soluble vitamins, and polyunsaturated fatty acids have proven well in experimental and clinical studies of influenza, pneumonia, and other respiratory disorders. The use of medications with antioxidant activity could be justified and most probably would increase the effectiveness of the fight against new coronavirus.

CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2.

Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of 193 female volunteers aged 45 to 60 years were divided into two groups: Those with BMI < 25 kg/m2 (control) and those with BMI ≥ 25 kg/m2. Each group was then divided into two subgroups: Those with the CLOCK TT-genotype and those with the CLOCK TC-, CC-genotypes. Lipid metabolism parameters were determined by the enzymatic method. Single-nucleotide polymorphisms (SNPs) were detected via polymerase chain reaction-restriction fragment length polymorphism technology. Results: There were no differences in CLOCK 3111T/C genotypes or allele frequency between the control and main groups. In addition, there were no differences in lipid profile parameters between women of the control group and different CLOCK 3111T/C genotypes. The total cholesterol (p = 0.041) and low-density lipoprotein cholesterol (p = 0.036) levels were higher in the subgroup of women with a BMI ≥ 25 kg/m2 and CLOCK TT-genotype as compared to the subgroup with a BMI ≥ 25 kg/m2 and minor allele 3111C. Conclusions: SNP 3111T/C of the CLOCK gene is not associated with BMI however, data suggest that the minor allele of the CLOCK 3111T/C gene polymorphism may have a protective role in atherogenic lipid levels in women with a BMI greater than or equal to 25 kg/m2.

The effect of low alcohol consumption during pregnancy on the lipid peroxidation-antioxidant defense system of women, their alcohol-exposed infants, and growth, health, and developmental outcomes.

BACKGROUND: Few studies have examined the effects of low-dose alcohol consumption on the "lipid peroxidation-antioxidant defense" (LPO-AOD) system of mothers and infants, and on infant growth and development. This study examined effects of alcohol consumption on the LPO-AOD system of pregnant women and newborns and infant development. METHODS: A total of 209 pregnant women were recruited for this prospective study at the first prenatal visit and followed until delivery: 112 consumed alcohol and 97 reported no alcohol use during pregnancy. Infants were evaluated at birth, and at 6 and 12 months of age. The study controlled for the confounding effect of maternal smoking. RESULTS: Biomarkers of lipid peroxidation, for example, thiobarbituric acid reactants, were higher and the activity of the antioxidant defense system was lower in drinkers and their infants. Higher rates of pathological conditions and slower postnatal growth were observed among infants who were prenatally exposed to alcohol. Low-dose alcohol use and tobacco smoking were associated with lower postnatal infant growth trajectories, resulting in restricted growth at 6 and 12 months among infants born to mothers who drank or smoked during pregnancy. Alcohol had a broad effect on the infant and maternal LPO-AOD system, while the effect of smoking was limited in this study to maternal glutathione peroxidase. CONCLUSIONS: Small amounts of alcohol consumed during pregnancy are associated with dysfunction of the LPO-AOD system and development of oxidative stress in women and their children. Identification and preventive interventions are needed for pregnant women who use alcohol in any amount.

Antioxidant status in peri- and postmenopausal women.

Menopause is a risk factor for oxidative stress. The aim of our study is to assess antioxidant system parameters (α-tocopherol, retinol, reduced glutathione, total antioxidant activity) in peri- and postmenopausal women. The antioxidant defense activity by estimation of total antioxidant activity, α-tocopherol, retinol, oxidized and reduced glutathione levels was studied in women of reproductive age (n=37), in perimenopausal (n=41) and postmenopausal women (n=41). In our study we used spectrofluorofotometer methods. Statistical analysis was performed by non-parametric tests with p<0.05 as the level of significance. The results of our study showed the decrease of α-tocopherol and retinol concentrations and the increase of oxidized glutathione level in blood serum both in perimenopausal and postmenopausal women, the total antioxidant activity of blood serum was decreased in postmenopausal women only. The results of our study demonstrate that decrease of antioxidant defense system resources depends on the menopausal phase.