Antioxidant System Parameters Research Articles

Rola stresu oksydacyjnego w patogenezie orbitopatii Gravesa

Streszczenie Choroba Gravesa-Basedowa (chGB) jest przewlekłą chorobą autoimmunologiczną, której auto-antygenem jest receptor TSH (TSHR) umiejscowiony na tyreocytach, a jego pobudzenie przez przeciwciała przeciwko TSHR (TRAb) powoduje nadmierne wytwarzanie hormonów tarczycy. TSHR wykazuje także ekspresję w tkankach pozatarczycowych, przede wszystkim w tkankach oczodołu, a stężenie TRAb w surowicy krwi dodatnio koreluje z ciężkością oraz aktywnością orbitopatii tarczycowej (OT). OT jest najczęstszym pozatarczycowym objawem chGB. Jest to choroba autoimmunologiczna, w której dochodzi do zmian zapalnych w obrębie tkanek oczodołów, tj.: mięśniach okoruchowych, tkance tłuszczowej oczodołu czy gruczole łzowym. Wzrost proliferacji fibroblastów oczodołowych i adipocytów oraz nadmierne wytwarzanie glikozaminoglikanów, obrzęk mięśni okoruchowych zwiększają objętość tkanek oczodołu i powodują powstanie objawów klinicznych choroby. Patogeneza OT jest złożona i nadal pozostaje niewyjaśniona. Fibroblasty oczodołów wykazują ekspresję TSHR, który jest głównym miejscem ataku autoimmunologicznego. Zgodnie z szeroko akceptowaną hipotezą po pobudzeniu receptorów dochodzi do aktywacji limfocytów T, które naciekając tkanki oczodołu stymulują je do wytwarzania cytokin, czynników wzrostu oraz wolnych rodników tlenowych (WRT). WRT powodują uszkodzenie wielu składowych komórki m.in. błony komórkowej przez peroksydację lipidów oraz białek doprowadzając do utraty ich funkcji i aktywności enzymatycznej. Stres oksydacyjny uaktywnia układ antyoksydacyjny działający poprzez dwa mechanizmy: enzymatyczny oraz nieenzymatyczny. Ocena stężenia markerów stresu oksydacyjnego oraz stężenia lub aktywności parametrów układu antyoksydacyjnego umożliwia ocenę nasilenia stresu oksydacyjnego, co w przyszłości może być wykorzystywane do oceny skuteczności leczenia i rokowania u chorych z aktywną OT.

The effect of acute strenuous exercise on some physiological, blood and antioxidant system parameters in Kangal shepherd dogs with and without ankyloglossia

The aim of this study was to investigate the effect of acute strenuous exercise on some physiological, blood and antioxidant system parameters in Kangal shepherd dogs with ankyloglossia. In both groups, red blood cell, leukocyte, hemoglobin, mean corpuscular volume, hematocrit levels along with superoxide dismutase enzyme activity and malondialdehyde levels were increased after acute strenuous exercise compared to before exercise. In both groups, the biochemistry parameters of total protein, albumin, glucose levels were decreased after acute strenuous exercise compared to before exercise. In both groups, the heart rate, respiratory rate, body temperature physiological values were increased after acute strenuous exercise compared to before exercise. In comparison of the groups within themselves after acute strenuous exercise, the respiratory rate and body temperature values were increased more in the ankyloglossial group. When the data obtained were evaluated, it was found that acute strenuous exercise affected physiological data more in the dogs with ankyloglossia. This study is the first study on blood and antioxidant system parameters in Kangal shepherd dogs with ankyloglossia.

The USE OF INDICATORS OF PLANT PHOTOSYNTHETIC AND ENZYMATICE ACTIVITY IN BIOINDICATION STUDIES

In the context of increasing anthropogenic impact on the environment, the study of the mechanisms of plant adaptation is an actual problem. To diagnose ecological troubles, it is advisable to study the indicators characterizing metabolic processes in autotrophic plants. The change in the parameters of the photosynthetic apparatus and antioxidant system in silver birch (Betula pendula), European spruce (Picea abies) and dandelion (Taraxacum officinale L.), depending on the intensity of anthropogenic load, was studied. The pigment composition of plants and the activity of antioxidant enzymes can be used as markers of the anthropogenic pollution level of a territory.

Hepatoprotective ability of tetramethylpyrazine produced by Bacillus amyloliquefaciens

Tetramethylpyrazine (TTMP), an important aroma compound, was produced by Bacillus amyloliquefaciens XJB-104 with distillers’ grains as raw material. The yield of TTMP under optimized fermentation procedure was 3176.52 mg/L. TTMP in the fermentation broth was purified and the purity (> 99%) was measured by gas chromatography–mass spectrometry. Furthermore, the hepatoprotective activity of TTMP in ethanol–water system was evaluated by biochemical indicators of liver injury, parameters of antioxidant defense system and inflammatory response, and liver histopathological assessment in mice. Ethanol treatment increased serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, suggesting liver damage. Both high and low dose of TTMP significantly decreased levels of these indicators. Furthermore, the reduction in the activities or concentrations of superoxide dismutase, catalase, reduced glutathione and malondialdehyde in liver tissue caused by ethanol was significantly alleviated by TTMP. Increased inflammatory cytokines including transcription factor, tumor necrosis factor, interleukin-1beta, interleukin, macrophage chemoattractant protein, inducible nitric oxide synthase and cyclooxygenase were also suppressed by TTMP treatment. It is concluded that TTMP in ethanol–water system has potential liver-protective activity, especially when ethanol is consumed at low doses for short periods of time.

The possible role of extra magnesium and nitrogen supply to alleviate stress caused by high irradiation and temperature in lemon trees

Citrus trees are subjected to variation of environmental conditions throughout the annual cycle, especially during the flowering and fruit set. Heat waves have affected the environmental conditions required for optimum crop growth and have reduced fruit yield and quality worldwide. This study aimed to evaluate an extra supply of magnesium (Mg) and/or nitrogen (N) to increase citrus tolerance to excessive increased irradiation and consequent air temperature. Young lemon trees were grown in a greenhouse with extra Mg, N and Mg + N supply for five months and then exposed to heat for 12 days. After imposing stress condition, photosynthetic and enzymatic antioxidant system parameters were assessed to evaluate the impact of the extra nutrient supply in alleviating stress induced by combination of elevated irradiance and air temperature. Extra nutrient supply increased plant tolerance to the environmental stress, allowing maintenance of high photosynthetic and transpiration rates and low ratio of apparent electron transport rate per photosynthetic carbon assimilated. Enhanced Mg supply also increased activity of the antioxidant enzyme system and decreased the oxidative stress of plants. Trees treated with extra N exhibited increased chlorophyll concentrations and ability to harvest light energy. Citrus trees under stressed condition, such as elevated air temperature and radiation, associated to heat waves, exhibited less damage in the photosynthetic mechanism and high activity of the antioxidant enzymatic system when supplied with extra nutrient. It was concluded that extra Mg and N supply are important tools to prevent damages and enhance lemon trees biochemical and physiological responses to alleviate the harmful effects of unfavorable environmental condition.

Are Heavy Metal Exposure and Trace Element Levels Related to Metabolic and Endocrine Problems in Polycystic Ovary Syndrome?

This study aimed to determine the relationship between the metabolic and endocrinological pathologies in polycystic ovary syndrome (PCOS) and the levels of arsenic, chromium, cadmium, lead, mercury, antimony, zinc, and copper to evaluate the relationship of these toxic metals with inflammatory/oxidative parameters. This study included a total of 154 patients (84 with PCOS, 70 healthy volunteers). Metabolic and endocrine parameters and arsenic, chromium, cadmium, lead, mercury, antimony, zinc, and copper serum levels of the patients were compared between the groups. Considering the action mechanism of toxic metals, serum malondialdehyde (MDA), superoxide dismutase (SOD), serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor-alpha (TNFα), and high-sensitivity C-reactive protein (HsCRP) levels were determined. Serum TAS (p = 0.002), OSI (p = 0.006), SOD (p = 0.006), zinc (p = 0.010), and copper (p = 0.030) values were statistically lower whereas TOS (p = 0.008), MDA (p < 0.001), HsCRP (p < 0.001), TNFα (p < 0.001), antimony (p < 0.001), cadmium (p < 0.001), lead (p < 0.001), and mercury (p < 0.001) levels were significantly higher in the PCOS group than those determined in the control group. Antimony was positively correlated with fasting glucose (FG) and HOMA-IR while cadmium, in addition to FG and HOMA-IR, positively correlated with insulin and lead had a positive correlation only with FG (p < 0.05). Also, these three heavy metals correlated positively with some oxidative system and inflammatory parameters and negatively with the antioxidant system parameters (p < 0.05). In conclusion, heavy metal exposures in PCOS may be related to insulin resistance and hirsutism through oxidative and inflammatory mechanisms. This approach can be used to identify the risky patient group and to develop new treatment modalities.

Effects of Acute Exhaustive Exercise on Oxidant and Antioxidant System Parameters in Rats with Streptozotocin Induced Diabetes Mellitus

Effects of Acute Exhaustive Exercise on Oxidant and Antioxidant System Parameters in Rats with Streptozotocin Induced Diabetes Mellitus

Role of Oxidant/Antioxidant Status in the Pathogenesis of Iron-Deficiency Anemia: Case Study on Children of Qalyubiyya and Minoufiya Governorates, Egypt

Iron- deficiency anemia (IDA) is anemia due to insufficient iron. It is one of the major causes of morbidity and mortality worldwide affecting people of all ages in both developed and developing countries. The present study aims to investigate the role of oxidative/antioxidant status in the pathogenesis of IDA through a case study on children of Qalyubiyya and Minoufiya Governorates, Egypt. 119 with IDA and 150 healthy control, boys and girls, infants and young children, aged zero months to 6 years, were selected for the study from Rural Health Units and Maternity and Child Care Centers, Qalyubiyya and Minoufiya Governorates, Egypt. Based on hematological and biochemical analysis, the mean hemoglobin (Hb) level, mean corpuscular volume (MCV), reticulocyte hemoglobin content, serum iron and serum ferritin were significantly lower in infants and young children with IDA than healthy control. The opposite direction was observed for the red blood cell distribution width (RDW). The antioxidant defense system parameters including [enzymes (glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Rd; superoxide dismutase, SOD and catalase, CAT) activities and none-enzymatic levels (glutathione, GSH and vitamins A, C and E)] of infants and young children with IDA were significantly (P≤0.05) lower. While the oxidative stress parameters thiobarbituric acid reactive substances, TBARS and nitric oxide, NO2 were significantly higher than the control group. In conclusion, oxidant/antioxidant status may play a role in the Pathogenesis of Iron-Deficiency Anemia.

How metals directly affect the antioxidant status in the liver and kidney of Oreochromis niloticus? An in vitro study

BackgroundMetals can disturb the integrity of physiological and biochemical mechanisms in fish. Thus components of defense as an antioxidant system are significant biomarkers due to their vital role in coping with metal stress. The aim of the current study is to investigate the direct effects of Cd, Cu, and Zn sublethal exposures (in vitro) on the antioxidant system parameters in the liver and kidney of Nile tilapia. MethodsThe antioxidant enzyme activities and GSH levels were analyzed after in vitro sublethal metal (200 and 400 μg/L Cd, Cu, and Zn) treatments of Oreochromis niloticus liver and kidney supernatants. ResultsMetals even at lower levels caused significant changes in the levels of antioxidant system parameters due to concentration, metal, and tissue type. GSH metabolism parameters were more responsive to the metal effect. TBARS levels and GPX activity were mostly increased while CAT, SOD, rGSH, and GSH/GSSG levels decreased. The kidney was more affected than the liver in vitro conditions. Cu was more effective in the liver whereas it was Zn for the kidney. Cd caused negative correlations among the antioxidant enzymes. Significant correlations were found between enzymes and GSH levels upon Zn and Cu exposures. ConclusionsDirect metal effects may trigger different response trends due to their nature and tissue differences. The current data provide a knowledge about which antioxidant biomarkers can define better the oxidative stress caused by direct metal effect for further studies including in vivo experiments.

Effects of Coenzyme Q10 on Some Blood Antioxidant System Parameters and Histological Changes in the Pancreas and Aorta of Streptozotocin-induced Diabetic Rats

Bu calismanin amaci diyabet olusturulan ratlarda koenzim Q10’un antioksidan parametreleri uzerine etkilerini degerlendirmektir. Calismada 38 yetiskin, erkek Wistar Abino rat (250-300 gr) kullanildi. Grup I’deki hayvanlara herhangi bir uygulama yapilmadi. Grup II’deki hayvanlara gunde 0.3 ml misir yagi dort hafta boyunca intraperitoneal olarak uygulandi. Grup III’deki hayvanlara gunde 0.3 ml misir yaginda cozdurulen 10 mg/kg CoQ10 dort hafta boyunca intraperitoneal olarak uygulandi. Grup IV’deki hayvanlarda, 40 mg/kg streptozotosinin gunde tek doz olmak uzere iki subkutan enjeksiyonu ile diyabet olusturuldu. Grup V’deki hayvanlarda ayni protokolle diyabet olusturuldu ve daha sonra bu hayvanlara dort hafta boyunca 0.3 ml misir yaginda cozdurulen 10 mg/kg CoQ10 intraperitoneal olarak uygulandi. Kan orneklerinde GSH, TBARS, SOD, NO seviyeleri ile GPx, CAT aktiviteleri belirlendi. Pankreas ve aorta doku ornekleri histolojik ve immunohistokimyasal yontemler kullanilarak incelendi. Diyabetik grupta plazma SOD, GPx, CAT ve GSH seviyeleri control grubuna gore onemli oranda dusuktu. Diyabetik ratlara CoQ10 uygulamasi ile bu parametreler diyabetik gruba gore onemli oranda artti. Diyabetle birlikte artan plazma TBARS seviyesi, CoQ10 uygulamasiyla azaldi. Calismanin histolojik bulgulari CoQ10 uygulamasi sonucunda enzim duzeylerindeki degisiklikleri desteklemektedir. Sonuc olarak, diyabetik ratlara CoQ10 uygulamasi diyabetin neden oldugu bazi olumsuz degisiklikler uzerine faydali etkilere sahip olabilir.

Deneysel Diyabette Döteryum Azlığının Eritrositler Üzerine Etkisi

In the development of diabetic complications, oxidative stress caused by hyperglycemia plays an important role. Deuterium depletion has protective effect against cellular damage and tumor suppressor effect in cancer cell lines. The purpose of this study was to examine and evaluate the effect of deuterium depletion on erythrocyte oxidant and antioxidant system parameters in experimental diabetes induced by streptozotocin (STZ) in rats. On the 30th or 40th day after STZ injection, blood samples were taken and blood glucose levels were measured. Erythrocyte hemolysates were also prepared. Lipid peroxidation and glutathione levels and glutathione-S-transferase, superoxide dismutase and catalase enzyme activities of erythrocytes were determined. At the 30 or 40 day periods, deuterium depleted water (DDW) consumption had differently affected oxidant-antioxidant parameters of erythrocytes. The clear effect of deuterium depletion in drinking water from 150 ppm to 85 ppm was observed in glutathione levels and it increased erythrocyte glutathione levels in both the control and diabetic groups. In conclusion, deuterium depletion may have protective effects on diabetes induced oxidative stress. Further studies are needed to be done to determine the mechanism of action and the useful dosage and the application period of DDW.

PECULIARITIES OF METABOLIC CHANGES IN EXPERIMENTAL ANIMALS AT EARLY TERMS OF PHARMACOLOGICAL CORRECTION OF TOXIC LIVER DISEASES

The paper presents the results of studies on metabolic changes in experimental animals with acute tetrachloromethane poisoning and further damage correction using substances possessing hepatoprotective properties: oxymethyluracil, ademethionine and ethylmethylhydroxypyridine succinate. It has been revealed that oxymethyluracil exhibits heteroprotective properties at the earliest stages of acute toxic liver damage with chemical toxicants: it has membrane-stabilizing properties, normalizes the levels of antioxidant system parameters, thereby restoring the oxidative-antioxidant balance in hepatocytes. Oxymethyluracil has more pronounced hepatoprotective properties at the early stages of treatment in comparison with ademethionine and ethylmethylhydroxypyridine succinate. The results obtained are important in terms of the prospective use of oxymethyluracil for the relief of hepatotoxic effects in acute exposure to hepatropic chemicals under environmental and industrial poisoning.

Combination of exercise and caloric restriction ameliorates nearly complete deleterious effects of aging on cardiovascular hemodynamic and antioxidant system parameters

Combination of exercise and caloric restriction ameliorates nearly complete deleterious effects of aging on cardiovascular hemodynamic and antioxidant system parameters

The influence of harmful physical factors and industrial dust on changes in some biochemical and functional indicators of the cardiovascular system and respiratory system in workers engaged in underground mining of ore

Introduction. The health of workers is determined by both social and individual, as well as production factors, including noise, vibration and dust, characteristic of technological processes in mining enterprises. Industrial noise above 90 dBA and dust in the form of suspended and fine particles causes dysfunction of the cardiovascular system and respiratory organs.The aim of the study is to assess the impact of harmful physical factors and industrial dust on changes in some biochemical and functional indicators of the cardiovascular system and respiratory system of employees of the enterprise for underground mining of ore.Materials and methods. The assessment of working conditions of workers engaged in underground mining and processing of chrome ores, the analysis of industrial dust on the dimension and quantitative content of fine particles PM10 and PM2. 5, the study of biochemical parameters of lipid metabolism, oxidant and antioxidant systems, indicators of respiratory function. Results. Harmful working conditions (class 3.1–3.4) in terms of noise and vibration were revealed at the workplaces of employees of the main specialties observation group. In the air of the working zone, the highest content of fine particles PM2.5 (2.68±0.54 mg/m3) and PM10 (4.64±0.93 mg/m3) was established at the site of drilling operations and cleaning of the bottom-hole space. Deviations of biochemical parameters characterizing intensification of free radical processes and antioxidant protection, imbalance of lipid spectrum parameters, and violation of functional parameters of external respiration were revealed. A high degree of connection with the working conditions of the frequency of increased levels of lipid hydroperoxide and antioxidant activity (EF=60.71–65.84%) was established.Conclusions. In high noise level (more than 94 dBA), general and local vibration (more than 116 and 127 dB respectively) and the content of fine particles PM2. 5 (more of 2.14 mg/m3) and PM10 (over of 3.71 mg/m3) at underground mining of chrome ore workers have identified abnormalities in the form of increase 1.6 times the level of lipid hydroperoxides and total antioxidant activity, reducing to 1.2 times the level of high density lipoprotein, improving 1.2–1.3 times of low-density lipoproteins, triglycerides, and atherogenic index in blood serum, peak expiratory flow. A high degree of professional conditioning have the frequency of increasing the level of lipid hydroperoxide in blood serum and antioxidant activity of blood plasma.

Galectin-1 exhibits a protective effect against hepatotoxicity induced by dextran sulfate sodium in mice.

Galectin-1 is an important mediator that regulates the T-cell-mediated immune response. It has many other biological functions such as cell growth, immunomodulation, and wound healing. The aim of this study was to reveal the role of galectin-1 on liver morphology, cell proliferation, apoptosis, inflammatory and anti-inflammatory mediators, oxidative stress, and antioxidant system in colitis-mediated hepatotoxicity induced by dextran sulfate sodium (DSS). In the present study, adult mice were divided into four groups: The control group intraperitoneally injected with phosphate buffer saline (I), the group which was orally administered with DSS (II), the control group which was injected with galectin-1 (III), and the group which was given DSS and galectin-1 (IV). DSS administration caused degenerative changes and diffuse necrotic damage, an increase in caspase-3 and cyclooxygenase-2 expression, the levels of lipid peroxidation and tumor necrosis factor-alpha, lactate dehydrogenase, and myeloperoxidase activities, and a decrease in cell proliferation, interleukin-10 levels, and antioxidant system parameters in liver tissues. Treatment of DSS group with galectin-1 reversed these effects and prevented liver damage. This study showed that galectin-1 has proliferative, antiapoptotic, anti-inflammatory, and antioxidant effects against DSS-induced liver injury in mice. It is expected considering all results of this study that galectin-1 may be useful as a protective agent against liver toxicity.

P.740 Reduced motivation to work for financial reward associated with harmful alcohol use in a community sample of young adults

In this study, Al2O3, CuO and TiO2 nanoparticles (NPs) were administered to mature female rats (Rattus norvegicus var. albinos) via oral gavage (0, 0.5, 5, 50 mg/kg b.w./day) for 14 days to investigate their effects on 14 serum biomarkers and 4 antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase) activities in the erythrocyte. Data showed that Al2O3 did not cause any significant (P > 0.05) change in the parameters, except few cases, while CuO and TiO2 caused significant alterations in antioxidant system parameters of the erythrocytes. Activities of catalase and superoxide dismutase significantly decreased in CuO and TiO2 administered rats. Oppositely, glutathione peroxidase activity increased in CuO and TiO2 administered rats. There were no significant alterations in the activity of glutathione S-transferase in the erythrocytes. Levels of glucose, cholesterol, bilirubin, triglyceride, triiodothyronine (T3), estradiol, prolactin and immunoglobulin M (IgM) in the serum altered after some of NP administrations, whereas cortisol, protein, creatinine, blood urea nitrogen (BUN), thyroxine (T4) and immunoglobulin G (IgG) levels in the serum did not change significantly after any of NP administration. There were outstanding increases in the levels of bilirubin and prolactin and decreases in the levels of triglyceride and estradiol. The present study demonstrated that the antioxidant enzymes in the erythrocyte were generally affected from copper and titanium NPs, while aluminium and copper NPs caused more significant alterations in serum biomarkers.

ОСОБЛИВОСТІ ЛІКУВАННЯ ХВОРИХ НА ХРОНІЧНИЙ БЕЗКАМ’ЯНИЙ ХОЛЕЦИСТИТ ІЗ СУПУТНЬОЮ ГІПЕРТОНІЧНОЮ ХВОРОБОЮ З УРАХУВАННЯМ ПОРУШЕНЬ В СИСТЕМІ ГОМЕОСТАЗУ

&#x0D; &#x0D; &#x0D; Recovery of chronic acalculous cholecystitis (CAC) in patients with hypetension disease (HD) is shown to be accompanied by inhibition of antioxidant system parameters and significant changes in lipid peroxidaton, which cause elevation of anti-inflammatiry cytokines level. The studied parameters correlate with thecharacterof the inflammatory processand the type of the gallbladder dyskinesia. The use of Choliver and Duspatalin in complex treatment of CAC in patients with HD provides clinical and laboratory remission, which allows to recommend these drugs for treatment of the above persons.&#x0D; &#x0D; &#x0D;

Lipid status and oxidative stress in menopausal women with obstructive apnea syndrome

to assess lipid profile, lipid peroxidation and antioxidant system parameters in peri - and postmenopausal women with obstructive sleep apnea syndrome (OSAS). 37 perimenopausal women and 43 postmenopausal ones were examined. OSAS diagnosis was made on the basis of the clinical picture and the polysomnography results. In perimenopause, the main group consisted of 18 women, in postmenopausal women - 17. All comparison groups are comparable by age and body mass index. Lipid profile, lipid peroxidation and antioxidant system parameters by spectrophotometric methods were determined. Non - parametric criteria were used to analyze the group differences for the independent samples. The increase of total cholesterol (TC) and low - density lipoprotein cholesterol (LDL-C) levels were observed in perimenopausal women with OSAS as compared to control. The increase of TC, triacylglycerol (TG), LDL-C, very - low - density lipoprotein cholesterol (VLDL-C) levels and decrease of high - density lipoprotein cholesterol (HDL-D) level were found in postmenopausal women with OSAS as compared to control. Accumulation of ketodienes and conjugated trienes in perimenopausal women with OSAS and thiobarbituric acid reactants with a decrease of total antioxidant activity of blood serum in postmenopausal women with OSAS as compared to control was observed. Moreover, postmenopausal women with OSAS have a higher lipid peroxidation substrates and diene conjugates levels with a lower α-tocopherol level and total antioxidant activity compared with perimenopausal patients.The integral indicator of oxidative stress assessment indicates an imbalance in the lipid peroxidation and antioxidant system in menopausal women with OSAS. The results obtained indicate a violation of lipid metabolism and the development of oxidative stress in patients with OSAS. This is most pronounced in the postmenopause due to the aggravation of the pathological condition.

The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70cm H2O. After a stabilization period, CPP was lowered to 60cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2-. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2- in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

Losartan effects on liver cytochromes CYP3A, CYP2C and CYP2E1 functioning at metabolic syndrome in young and adult rats

CYP450-dependent interactions and toxicological consequences of hypoglycemic and antihypertensive drugs used in treatment of children with metabolic syndrome (MS) remained unclear. Our aim was to carry out a complex estimation of metabolic syndrome and losartan mediated changes in CYP3A, CYP2C, CYP2E1 mRNA expression, corresponding marker enzymes activities, liver antioxidant system and lipid peroxidation parameters of adult and pubertal rats. Wistar albino male rats of two age categories (young animals of 21 days age (50–70 g) and adults (160–180 g) were divided into 6 groups (6 animals in each): 1 – Control 1 (intact young rats); 2 – Control 2 (intact adult rats); 3 –young rats with MS; 4 – adult rats with MS; 5 – young rats with MS+losartan; 6 – adult rats with MS+ losartan. The metabolic syndrome model was induced by full replacement of drinking water with 20% fructose solution (200 g/l). After 60 days of MS modeling, investigation of rat liver CYP3A, CYP2C, CYP2E1 mRNA expression, their marker enzymes activities, lipid peroxidation parameters were carried out. Losartan administration caused increase of CYP3A, CYP2C and CYP2E1 mRNA expression rates in both age groups. Marker enzymes, glutathione transferase and reductase rates were normalized only in adult rats. In group of pubertal animals losartan administration led to CYP3A and CYP2C marker enzymes activities normalization. Liver reduced glutathione contents remained decreased in both age groups. Thus, losartan demonstrates some age-dependent effectiveness towards normalization of CYP450 isoforms expression rates, p-nitrophenol hydroxylase, erythromycin-N-demethylase and diclofenac hydroxylase activities, but not glutathione system and lipid peroxidation rates.