Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity., J. Hrenák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension., D. Hodyc ... [et al.]., and Obsahuje seznam literatury
We studied the response of several parameters related to oxidative stress in the liver of aging rats. Male Wistar rats aged 1.5, 3, 18 and 24 months were used. Livers showed an increase in superoxide anion (O2-) concentration at 1.5 and 18 months of age compared to the 3-month-old group; a decrease in superoxide dismutase (SOD) was seen at 1.5 months and catalase concentrations remained unaltered throughout the aging process. Nitric oxide (NO) progressively declined with age; a significant decrease was particularly apparent at 18 and 24 months of age. Thiobarbituric acid reactive substances (TBARS) decreased significantly at 1.5 months, whereas it increased at 18 and 24 months of age. Concentrations of prostaglandin E2 (PGE2), and adenine nucleotides, and their metabolites, remained unchanged throughout the aging process. Although the mitochondrial damage caused by oxidative stress can result in reduced ATP production and compromised cell function, our results on adenosine nucleotides and their metabolites support the notion that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. In conclusion, we observed a significant decrease in the levels of NO in the older groups of rats and hence in its antioxidant activity. This could explain the observed increase in lipid peroxides which suggests an important role for NO in oxidative stress in the liver of older rats., F. Mármol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The study of ischemia/reperfusion injury included 25 patients in the acute phase of myocardial infarction (19 perfused, 6 remained non-reperfused as evaluated according to the time course of creatine kinase and CK-MB isoenzyme activity) and a control group (21 blood donors). Plasma level of malondialdehyde was followed as a marker of oxidative stress. Shortly after reperfusion (within 90 min), a transient increase of malondialdehyde concentration was detected. The return to the baseline level was achieved 6 h after the onset of therapy. The activity of a free radical scavenger enzyme, plasma glutathione peroxidase (GPx), reached its maximum 90 min after the onset of treatment and returned to the initial value after 18 h. The specificity of the GPx response was confirmed by comparing with both non-reperfused patients and the control group, where no significant increase was detected. The erythrocyte Cu,Zn-superoxide dismutase (SOD) did not exhibit significant changes during the interval studied in perfused patients, probably due to the stability of erythrocyte metabolism. In non-reperfused patients, a decrease of SOD was found during prolonged hypoxia. These results help to elucidate the mechanisms of fast activation of plasma antioxidant system during the reperfusion after myocardial infarction., V. Mužáková, R. Kanďár, P. Vojtíšek, J. Skalický, Z. Červinková., and Obsahuje bibliografii
Oxidative stress is a phenomenon associated with pathogenetic mechanisms of several diseases including atherosclerosis, neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, cancer, diabetes mellitus, inflammatory diseases, as well as psychological diseases or aging processes. Oxidative stress is defined as an imbalance between production of free radicals and reactive metabolites, so-called oxidants, and their elimination by protective mechanisms, referred to as antioxidative systems. This imbalance leads to damage of important biomolecules and organs with potential impact on the whole organism. Oxidative and antioxidative processes are associated with electron transfer influencing the redox state of cells and the organism. The changed redox state stimulates or inhibits activities of various signal proteins, resulting in a changed ability of signal pathways to influence the fate of cells. At present, the opinion that oxidative stress is not always harmful, has been accepted. Depending on the type of oxidants, intensity and time of redox imbalance as well as on the type of cells, oxidative stress can play a role in the regulation of other important processes through modulation of signal pathways, influencing synthesis of antioxidant enzymes, repair processes, inflammation, apoptosis and cell proliferation, and thus processes of malignity. Imprudent administration of antioxidants may therefore have a negative impact on the organism., Z. Ďuračková., and Obsahuje bibliografii a bibliografické odkazy
An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by bodyplethysmography. Moderate COPD (FEV1 50-80 %) was present in 23, and severe COPD (FEV1 < 50 %) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1±1.5 vs. 47.7±2.9 U/gHb, p<0.05, MDA: 2.4±0.1 vs. 2.1±0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD., Z. Kluchová, D. Petrášová, P. Joppa, Z. Dorková, R. Tkáčová., and Obsahuje bibliografii a bibliografické odkazy
The aim of our work was to compare the effect of D-galactosamine (GalN) on primary cultures of lean and steatotic rat hepatocytes isolated from intact and fatty liver, respectively. GalN caused more severe injury to steatotic hepatocytes than to lean cells as documented by lactate dehydrogenase leakage. Necrotic mode of cell death strongly prevails over apoptosis since we did not observe any significant increase in activities of caspase 3, 8 and 9 in any group of hepatocytes treated with GalN. Reactive oxygen species (ROS) formation and lipid peroxidation were elevated in a dose-dependent manner by GalN and were significantly more pronounced in fatty hepatocytes. A decrease in the percentage of hepatocytes with energized mitochondria was observed from 30 mM and 10 mM GalN in lean and steatotic hepatocytes, respectively. Our results undoubtedly indicate that steatotic hepatocytes exert higher sensitivity to the toxic effect of GalN. This sensitivity may be caused by more intensive GalN-induced ROS production and lipid peroxidation and by higher susceptibility of mitochondria to loss of mitochondrial membrane potential in steatotic hepatocytes. In our experimental arrangement, apoptosis does not seem to participate considerably on hepatotoxic action of GalN in either group of hepatocytes., O. Kučera, H. Lotková, O. Sobotka Z. Červinková., and Obsahuje bibliografii
Cholestasis is characterized by the elevation of serum total bile acids (TBA), which leads to the production of both free radicals and oxidative stress. Although they do not share the same mechanisms, membrane glycosphingolipids (GSL) and the antioxidant enzyme heme oxygenase-1 (HMOX1) both act against the pro-oxidative effect of TBA. The aim of the study was to assess the role of HMOX on GSL redistribution and composition within hepatocytes in the rat model of estrogen-induced cholestasis. Compared to the controls, an increase of total gangliosides in the liver homogenates of the cholestatic group (P=0.001) was detected; further, it paralleled along with the activation of their biosynthetic b-branch pathway (P<0.01). These effects were partially prevented by HMOX activation. Cholestasis was accompanied by a redistribution of GM1 ganglioside from the cytoplasm to the sinusoids; while HMOX activation led to the retention of GM1 in the cytoplasm (P=0.014). Our study shows that estrogen-induced cholestasis is followed by changes in the synthesis and/or distribution of GSL. These changes are not only triggered by the detergent power of accumulated TBA, but also by their pro-oxidant action. Increases in the antioxidant defenses might represent an important supportive therapeutic measure for patients with cholestatic liver disease., T. Petr, V. Šmíd, V. Kučerová, K. Váňová, M. Leníček, L. Vítek, F. Šmíd, L. Muchová., and Obsahuje bibliografii
Several authors have reported the association of postprandial hypertriglyceridemia with oxidative stress, systemic inflammation and endothelial dysfunction. Our aim was to investigate the effect of high-calorie meal on blood markers of oxidative stress and endothelial dysfunction and the association of APOA5-1131T/C and -250G/A hepatic lipase (HL) polymorphisms with postprandial triglyceride response. This study included 102 healthy male volunteers. All participants consumed a high-calorie meal (823 calories, 50 g fat, 28 g protein, 60 g carbohydrates). Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, hsCRP, TAS and ICAM-1 were measured at fasting state and postprandially. APOA5-1131T/C and -250G/A HL polymorphisms were also determined. Postprandial triglycerides were significantly increased (1.4 (1.1-2.1) vs. 2.4 (1.9-3.3) mmol/l, P<0.001). Average triglyceride increase was 1.0±0.7 mmol/l (65 %). Concentration of triglycerides, HDL- cholesterol, LDL-cholesterol, TAS and ICAM-1 differed significantly between the fasting state and postprandial measurements (P<0.001). However, those differences were within the limits of analytical imprecision. Other parameters did not change 3 h after the meal. Triglycerides response did not differ respective to the APOA5 and HL polymorphisms. Family history of hypertension and acut e myocardial infarction were associated with higher postprandial triglyceride concentrations. Postprandial hypertriglyceridemia is not associated with increased concentrations of hsCRP, TAS and ICAM-1. Furthermore, APOA5-1131T/C and -250G/A HL polymorp hisms are not associated with different postprandial triglyceride response., S. Kackov ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The aim of this work was to establish and characterize a nutr itional model of NAFLD in rats. Wistar or Sprague-Dawley male rats were fed ad libitum a standard diet (ST-1, 10 % kcal fat), a medium-fat gelled diet (MFGD, 35 % kcal fat) and a high-fat gelled diet (HFGD, 71 % kcal fat) for 3 or 6 weeks. We examined the serum biochemistry, the hepatic malondialdehyde, reduced glut athione (GSH) and cytokine concentration, the respiration of liver mitochondria, the expression of uncoupling protein-2 (UCP-2) mRNA in the liver and histopathological samples. Feeding with MFGD and HFGD in Wistar rats or HFGD in Sprague-Dawley rats induced small-droplet or mixed steatosis without focal infl ammation or necrosis. Compared to the standard diet, there were no significant differences in serum biochemical parameters, except lower concentrations of triacylglycerols in HFGD and MFGD groups. Liver GSH was decreased in rats fed HFGD for 3 weeks in comparison with ST-1. Higher hepatic malondialdehyde was found in both strains of rats fed HFGD for 6 weeks and in Sprague-Dawley groups using MFGD or HFGD for 3 weeks vs. the standard diet. Expression of UCP-2 mRNA was increased in Wistar rats fed MFGD and HFGD for 6 weeks and in Sprague-Dawley rats using HFGD for 6 weeks compared to ST-1. The present stud y showed that male Wistar and Sprague-Dawley rats fed by HFGD developed comparable simple steatosis without signs of progression to non-alcoholic steatohepatitis under our experimental conditions., O. Kučera ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy