Levels Of Lipid Peroxidation Products Research Articles

Effects of rutin on the physicochemical properties of skin fibroblasts membrane disruption following UV radiation

Human skin provides the body's first line of defense against physical and environmental assaults. This study sought to determine how rutin affects the membrane electrical properties, sialic acid content, and lipid peroxidation levels of fibroblast membranes after disruption by ultraviolet (UV) radiation. Changes in cell function may affect the basal electrical surface properties of cell membranes, and changes can be detected by electrokinetic measurements. The charge density of the fibroblast membrane surface was measured as a function of pH. A four-component equilibrium model was used to describe the interaction between ions in solution and ions on the membrane surface. Agreement was found between experimental and theoretical charge variation curves of fibroblast cells between pH 2.5 and 8. Sialic acid content was determined by Svennerholm's resorcinol method, and lipid peroxidation was estimated by measuring the malondialdehyde level. Compared to untreated cells, ultraviolet A (UVA)- or ultraviolet B (UVB)-treated skin cell membranes exhibited higher concentrations of acidic functional groups and higher average association constants with hydroxyl ions, but lower average association constants with hydrogen ions. Moreover, our results showed that UVA and UVB radiation is associated with increased levels of sialic acid and lipid peroxidation products in fibroblasts. Rutin protected cells from some deleterious UV-associated membrane changes, including changes in electrical properties, oxidative state, and biological functions.

ВПЛИВ ІОНІВ КАДМІЮ ТА ЕСЕНЦІАЛЬНИХ НАНОМЕТАЛІВ НА ФІЗІОЛОГО-БІОХІМІЧНІ ПАРАМЕТРИ РОСЛИН САЛАТУ ПОСІВНОГО

Due to the aim the effect of pre-sowing treatment with a nonionic colloidal solution of the mix of copper, zinc, manganese and iron nanoparticles, cadmium ions and their combined action on the physiological and biochemical indices: the content of lipid peroxidation products and balance of photosynthetic pigments in green Lolo and red Lolo Ross varieties of Lactuca sativa L. was investigated. Spectrophotometric methods of investigating the content of peroxides, thiobarbiturate-active products (with use of the modified Kumar and Knowles method), as well as the content of the main photosynthetic pigments (chlorophyll a, b, a/b ratio, and the carotenoid content) with the Wintermans, de Mots calculations application were used. Due to the results, a decrease in the content of peroxides and growth of malonic dialdehyde was observed for most treatment variants of Lolo. The opposite tendency was observed for the Ross variety (the initial growth of these parameters under the nanoparticles influence decreased to the control during the fourteen-day exposure). The decrease of chlorophyll content was observed In the Lolo variety under the essential metal nanoparticles influence, in contrast to the action of cadmium.For the Ross variety, a significant reduction of both chlorophyll and carotenoid contents in all treatment types during exposure was calculated.The a/b-index for Lolo plants has significantly increased in variants of cadmium influence, for Ross plants the divergence of the influence of all treatment variants has been marked. As a result, the treatment with a mixture of essential nanometals showed additive stress-loading functions. It was observed in a growth of the level of lipid peroxidation products and the reduction of the photosynthetic pigment biomarkers in both varieties during the 0,1 mM cadmium exposure. The Lolo Ross variety showed a higher variability of results under different treatment, compared to the Lolo variety.

In vivo effects of hemin and nitric oxide donors on parameters of heme metabolism in rat liver and serum

In vivo effects of hemin chloride (15 mg/kg body weight) and donors of nitrogen monoxide (NO) – sodium nitroprusside (SNP, 1 mg/kg) and substrate of NO-synthase L-arginine (L-Arg, 600 mg/kg) on the activity of key enzymes of heme synthesis (5-aminolevulinate synthase, ALAS) and heme degradation (heme oxygenase, HO), on the free heme level in liver and on the content of heme in blood serum of rats were studied. NO donors were administered alone or 30 min before hemin chloride injection. The level of free heme in liver was estimated by the ratio of holoenzyme and total tryptophan 2,3-dioxygenase (TDO) activities. Two hours after hemin chloride administration a significant increase in the level of heme-containing products and lipid peroxidation products (TBARS) was found in blood serum. These changes were accompanied by decrease in ALAS activity and by increase in holoenzyme activity and heme saturation of TDO, which was the result of free heme accumulation in liver. 24 hrs after administration of hemin chloride the content of heme in serum returned to normal level, while level of TBARS remained elevated. 24 hrs after hemin action a significant increase in the activities of HO and ALAS was observed in liver, while the degree of TDO heme saturation decreased, indicating the prevalence of heme degradation over its synthesis. Both NO donors did not affect the accumulation of heme in serum and liver first hours after hemin action. However, the specific features of SNP and L-Arg effects on the key enzyme of heme synthesis in liver and the TBARS level in serum were revealed. L-Arg, unlike SNP, prevented the accumulation of TBARS in serum, but did not prevent a decrease in ALAS activity 2 hrs after hemin chloride injection. The treatment by SNP itself caused an increase in TBARS level in serum, an increase in TDO activity and a decrease in ALAS activity in liver 2 hrs after action. Heme content in serum positively correlated with holoenzyme activity and heme saturation of TDO in liver. The pretreatment with NO donors did not affect the increase in HO activity, however, it blocked the induction of ALAS, a decrease in holoenzyme activity and heme saturation of TDO 24 hrs after the administration of hemin chloride. Thus, both SNP and Arg prevented a decrease in free heme level in liver, which might be due to heme nitrosylation in the presence of NO donors and, as a result, its slower degradation in the heme oxygenase reaction.

Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats following oral exposure.

The present study aimed to evaluate the effect of Copper Oxide (CuO) Nanoparticles (NP) on liver following oral exposure in rats. A total of 18 male wister rats were used in the experiments including a control group (6 rats). NP were given to the rats with a doses (5, 50 mg/kg b.w./day) via oral gavage and a control group (received only 200 μl PBS). The treatment was continued for 14 days. The supernatants of rat Liver tissue homogenates were used to analyze for glutathione levels (GSH), Catalase, superoxide dismutase (SOD), the extent of lipid peroxidation products (Malondialdehyde, MDA). Oral administration of NP to rats caused a significant (P < 0.05) dose dependent alterations in antioxidant enzyme activities. Data results clearly showed the significant decrease (p < 0.05) in GSH, Catalase (CAT) and SOD activity, whereas the lipid peroxidation product (MDA) levels were increased (p < 0.05). In conclusion, oral exposure of CuO nanoparticles to rats causes significant toxicity to the liver and it might be due to oxidative stress.

Effects of dietary oxidized fish oil supplementation on oxidative stress and antioxidant defense system in juvenile rainbow trout (Oncorhynchus mykiss)

The objective of the study was to characterize the response of the antioxidant defense system against dietary prooxidant conditions in rainbow trout juveniles. Fish (initial mean weight: 62 ± 1 g) were fed three fishmeal and plant-derived protein-based diets supplemented with 15% fresh fish oil (CTL diet), 15% fresh fish oil from tuna by-products (BYP diet) or 15% autooxidized fish oil (OX diet) over a 12-week growth trial at 17.5 ± 0.5 °C. No significant differences in growth performance were recorded between dietary groups. Muscle lipid content was reduced and n-6 PUFA levels were increased in rainbow trout fed diets BYP and OX compared to CTL. After 12 weeks of feeding, the level of lipid peroxidation products in muscle was not affected whereas the 8-isoprostane content in liver was increased in fish fed diet OX as well as plasma total and oxidized glutathione contents. The hepatic and muscle contents for α-tocopherol were decreased in fish fed BYP and OX. Hepatic antioxidant enzyme activities and mRNA levels were not affected after 12 weeks of feeding, except for catalase and glutathione peroxidase 1b2 mRNA levels that were decreased in trout fed diet OX. Fish fed diet OX and BYP displayed also reduced cytosolic Nrf2 and both cytosolic and nuclear NF-κB protein levels in liver. The present work indicates that feeding rainbow trout juveniles with fresh fish oil from by-products or moderately oxidized lipid appears not to be detrimental to the growth performance of fish. The mechanisms beyond the control of the antioxidant defense system by moderately oxidized lipid require further investigations in rainbow trout juveniles.

ВЛИЯНИЕ ОРГАНИЧЕСКИХ ФОРМ ЙОДА И ЦИНКА НА СООТНОШЕНИЕ ПРООКСИДАНТНЫХ И АНТИОКСИДАНТНЫХ СИСТЕМ ОРГАНИЗМА ПРИ ЙОДНОЙ НЕДОСТАТОЧНОСТИ

The lack of microelements and the development of hypo-microelementoses lead to suppression of the antioxidant system, represented by enzymatic and non-enzymatic components and intensification of oxidative stress. In particular, during the dysfunction of the thyroid gland caused by lack of iodine intake, the level of lipid peroxidation products and the intensity of formation of reactive oxygen species changes and an imbalance in the pro- and anti-oxidant system occurs. In this work, pro- and antioxidant systems of the animal organism in conditions of iodine deficiency under experimental hypothyroidism and subsequent correction with organic forms of iodine and zinc were studied. The state of the antioxidant system of the experimental animals was assessed by the amount of reduced glutathione, the activity of glutathione peroxidase and the total content of antioxidants in serum. The degree of development of oxidative processes in the body was assessed by the accumulation of malonic dialdehyde. In experiments involving 30 non-native white male rats, it was found that experimental hypothyroidism (25 mg / kg of tyrosol for 14 days) caused an intensification of the processes of peroxidation and inhibition of both the enzyme and non-enzyme links of the antioxidant system. The introduction of the investigated microelement organic forms restored not only the level of thyroid hormones, but also inhibited the processes of lipid peroxidation, while restoring the activity and level of enzyme and non-enzyme antioxidants.

Marantodes pumilum (Kacip fatimah) enhances in-vitro glucose uptake in 3T3-L1 adipocyte cells and reduces pancreatic complications in streptozotocin-nicotinamide induced male diabetic rats

Marontades pumilum is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), however the underlying mechanisms were not fully identified. In this study, we hypothesized that M. pumilum could help to enhance cellular glucose uptake and reduces pancreatic complications, which contributed towards its beneficial effects in DM. MethodsTwo parameters were measured (i) rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by levels of pancreatic oxidative stress, inflammation and apoptosis. In the meantime, phyto-chemical compounds in M.P were also identified by using LC–MS. ResultsM.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells in-vitro while its administration to the male diabetic rats causes decreased in the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes increased in insulin and high-density lipoprotein (HDL) levels, to near normal. Levels of oxidative stress in the pancreas as reflected by levels of lipid peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as reflected by NF-κB p65, Ikkβ and TNF-α levels decreased while apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti-apoptosis marker, Bcl-2 levels in pancreas increased. ConclusionsThe ability of M.P to enhance glucose uptake and reduces pancreatic complications could account for its beneficial effects in treating DM.

Показники прооксидантно-антиоксидантної системи печінки при експериментальному антифосфоліпідному синдромі та застосуванні L-аргініну

Introduction. Antiphospholipid syndrome (APS) that is developed due to underlying autoimmune mechanism often causes miscarriage, vessels thrombosis of different localization, cerebrovascular accident, cardiovascular and other diseases that are accompanied by significant activation of free radical processes. Pathogenesis of liver damage in cases of APS has not been adequately studied.The aim of the study – to establish the changes in parameters of prooxidative-antioxidant system and tissue respiration in liver in cases of experimental antiphospholipid syndrome and L-arginine administration.Research Methods. Mice of BALB/c line were used in the research. The APS was modeled using cardiolipin emulsified in 75 complete Freund's adjuvant; subsequent injections were administered with incomplete Freund's adjuvant. Cardiolipin was injected intramuscularly four times at a dose of 30 µg per 1 injection with 14-day intervals between the injections. For correction, L-arginine hydrochloride (25 mg/kg) was administered once daily during 10 days after APS development.The activity and content of antioxidant system components (superoxide dismutase, catalase, reduced glutathione) were investigated in liver tissue. The level of lipid peroxidation products was determined by the content of lipid hydroperoxides and TBA-active products. The state of energy-supplying processes of mitochondria was studied due to the activity of succinate dehydrogenase and cytochrome oxidase. The concentration of proteins was determined by Lowry method.Results and Discussion. In cases of APS in liver the imbalance in functioning of prooxidative antioxidant system (increased activity of superoxide dismutase and catalase, decrease in the content of reduced glutathione, increase in the level of lipids hydroperoxides, TBA-active products), of mitochondrial electron transport chain (decrease in the activity of succinate dehydrogenase, cytochrome oxidase) in cases of experimental antiphospholipid syndrome was evidenced. In cases of experimental APS in presence of L-arginine administration, the re-establishment of activity and content of antioxidant system components, enzymes of mitochondrial electron transport chain, decrease in content of lipid hydroperoxides and TBA-active products in liver was proved.Conclusion. In cases of experimental antiphospholipid syndrome, L-arginine, in the event of its repeated administration, reduces manifestations of oxidative stress and reactivate enzymes of mitochondrial electron transport chain in liver tissue of BALB/c mice.

Resveratrol suppresses ethanol stress in winery and bottom brewery yeast by affecting superoxide dismutase, lipid peroxidation and fatty acid profile.

Mid-exponential cultures of two traditional biotechnological yeast species, winery Saccharomyces cerevisiae and the less ethanol tolerant bottom-fermenting brewery Saccharomyces pastorianus, were exposed to different concentrations of added ethanol (3, 5 and 8%) The degree of ethanol-induced cell stress was assessed by measuring the cellular activity of superoxide dismutase (SOD), level of lipid peroxidation products, changes in cell lipid content and fatty acid profile. The resveratrol as an antioxidant was found to decrease the ethanol-induced rise of SOD activity and suppress the ethanol-induced decrease in cell lipids. A lower resveratrol concentration (0.5mg/l) even reduced the extent of lipid peroxidation in cells. Resveratrol also alleviated ethanol-induced changes in cell lipid composition in both species by strongly enhancing the proportion of saturated fatty acids and contributing thereby to membrane stabilization. Lower resveratrol concentrations could thus diminish the negative effects of ethanol stress on yeast cells and improve their physiological state. These effects may be utilized to enhance yeast vitality in high-ethanol-producing fermentations or to increase the number of yeast generations in brewery.

182 - Oxidative Stress Parameters in Adolescent Boys with Exogenous-Constitutional Obesity

Background Child and adolescent obesity have special attention, since, it is beginning in adolescence, it is progressing and leading to the development of complications already in the adult state. One of the leading mechanisms of the pathogenesis of obesity is the activation of oxidative stress reactions, with decreased activity of antioxidant factors. Methods The state of lipid peroxidation processes in 42 adolescent boys was assessed, 19 of them were diagnosed with exogenous-constitutional obesity. Spectrophotometric and fluorometric methods were used. Results Decreased levels of primary lipid peroxidation products - diene conjugates (1.39 times) and increased concentration of secondary products - ketodienes and conjugated trienes (1.65 times) in adolescent boys with obesity were registered. In the antioxidant defense system were noted reduced values of α-tocopherol (1.42 times), retinol (1.51 times) and superoxide dismutase activity (1.19 times), in the absence of statistically significant changes in the total antioxidant activity content blood and components of glutathione status in adolescent boys with obesity in comparison with control. Conclusion Exogenous-constitutional obesity adolescent boys were exposed to more oxidative stress than adolescent boys with normal weight. Increased systemic oxidative stress induced by childhood obesity can cause development of obesity-related complications and diseases.

181 - The Correlation between Antioxidant Deficiency and Reproductive Disorders in Women with HIV-infection

Background An evaluation of oxidative stress and antioxidant defense activity parameters in patients with HIV-infection is of great importance, especially for HIV-positive women of reproductive age planning to have children. The aim of this study was to identify antioxidant deficiency and frequency of reproductive disorders correlation in women with HIV-infection. Methods 53 women with HIV infection (mean age - 31.13 ± 4.49 years) were included in the investigations. They were divided into four groups depending on vitamins in blood plasma content (36 women - α-tocopherol level less than 12 μmol/L (group 1); 17 women α-tocopherol level in the range 12-24 μmol/L (group 2); 35 women with retinol level less than 1.05 μmol/L (group 3) and 18 women – retinol level in the range 1.05-2.8 μmol/L (group 4). Spectrophotometric and fluorometric methods used. Results Our study proved that women with HIV and α-tocopherol deficiency have higher level of the reproductive system disorders (incidence of menstrual disorders (63%), infertility (36.1%), and a high percentage of failure of the luteal phase) than in the group with normal vitamin content. Increased levels of primary lipid peroxidation products - diene conjugates (1.8 ± 0.9 μmol/L in group 1 patients than those in group 2 (1.3 ± 0.7 μmol/L) (p=0.043), with the absence of significant differences in the content of the thiobarbituric acid reactants in this group were registered. Conclusion The results obtained showed a close correlation of α-tocopherol deficiency and disorders of the reproductive system in women with HIV-infection. It is a significant reason to recommend including of antioxidant drugs in HIV-women patients of complex pathogenetic therapy to regulate adequately their reproductive function and possibly to preserve reproductive ability in these women.

Prooxidant–antioxidant system and change of alkaloids level in jimson weed (Datura stramonium L.) under the influence of static magnetic field

The effect of magnetic radiation on the prooxidant-antioxidant system and alkaloids level in Jimson weed (Datura stramonium L.) have never been studied and reported before. The objective of this research was to study the influence of static magnetic field on the homeostasis and alkaloids level in D. stramonium. The level of (thio) barbituric acids active products, superoxide dismutase and catalase activity in D. stramonium seedlings under the influence of static magnetic field with the intensity of 3 mT and 10 mT at two exposure times, 30 min and 22&nbsp;hours, was studied. Under these conditions, the level of alkaloids in the extract from leaves and stems of germs was determined by chromatographic analysis. An increased level of lipid peroxidation products, the activity of superoxide dismutase and catalase in seedlings under the long-term effect of magnetic field were observed. The level of scopolamine alkaloid depended on the duration of exposure to the static magnetic field; however, this factor did not effect the atropine level. The obtained experimental data was confirmed by the results of the analysis of variance.

The viability of primary hepatocytes is maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production

Extracellular cystine, the oxidized form of cysteine (Cys), is taken up by cells via the cystine transporter xCT. xCT is not expressed in the liver but is induced in primary hepatocytes under conventional cultured conditions. However, compared to wild-type hepatocytes those from the xCT-knockout mouse showed no evidence of an abnormality and the levels of both Cys and glutathione (GSH) remained unchanged. The levels of ophthalmic acid (OPT), which is produced as an alternative compound by the GSH-synthesizing pathway, became increased during the culturing of hepatocytes. It therefore appears that, in primary hepatocytes, Cys is provided by systems other than xCT, most likely via the transsulfuration pathway, but the levels that are produced are not sufficient. We also employed mouse hepatoma-derived Hepa1-6 cells, which constitutively express xCT. When Hepa 1-6 cells were cultivated in Cys-free media, the levels of intracellular Cys and GSH were decreased, compared to cells cultured in conventional media, leading to cell death accompanied by an increase in the levels of reactive oxygen species and lipid peroxidation products with characteristics similar to ferroptosis. While OPT levels were increased by only to a limited extent in Hepa 1-6 cells, primary hepatocytes cultured in Cys- and Met-free media showed a marked elevation in OPT, reaching levels nearly equivalent to the GSH levels when the cells were cultured in conventional media. Thus, OPT may become a marker for Cys insufficiency and might be used to predict pathological conditions of cells with elevated oxidative stress.

The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex.

Depressive disorders are associated with oxidative stress. Therefore, it is interesting if antidepressants can affect redox equilibrium and signaling. The first step of our study was to determine the influence of the adenosine system on the antidepressant-like activity of noncompetitive antagonist of the NMDA (N-methyl-d-aspartate) receptor complex - dizocilpine (MK- 801). To this aim, two behavioral tests commonly used to assess the antidepressant capability of drugs - the forced swim test (FST) and tail suspension test (TST), were performed. Locomotor activity was estimated to verify and exclude false positive/negative results in the FST and TST. To examine whether antidepressants affect redox equilibrium, we have investigated lipid peroxidation products (LPO), GSH (glutathione), GSSG (glutathione disulfide), NADP+ (nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate) in the cerebral cortex of mice following administration of CPT (8-cyclopentyl-1,3-dimethylxanthine) and MK-801 (dizocilpine) under environmental stress conditions. The experiments were carried out using male Albino Swiss mice (25-30 g). The drugs were administered ip., alone and simultaneously, 60 min before tests. The behavioural tests results showed that CPT (3 mg/kg) potentiated the antidepressant-like activity of MK-801 (0.05 mg/kg) and the observed effects were not due to the increase in mice locomotor activity. Positive synergism of CPT and MK-801 in reduction of environmental stress conditions was revealed. In this group an increase in GSH and GSSG without changes in GSH/GSSG ratio and reduction of LPO was found. The level of lipid peroxidation products was also decreased in group receiving CPT and MK-801 separately. Examined antidepressant agents may increase antioxidant defences however further studies are needed with different range of time.

Administration of mesenchymal stromal cells before renal ischemia/reperfusion attenuates kidney injury and may modulate renal lipid metabolism in rats

Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodent models. The mechanisms of such nephro-protection remain largely unknown. Furthermore, the optimal timing of MSC administration has been poorly investigated. Here, we compare the impact of MSC injection 7 days before (MSCD − 7) versus 1 day after (MSCD + 1) renal I/R in rats. Control groups received equivalent volumes of saline at similar time-points (SD − 7 and SD + 1). Right nephrectomy was performed, and left renal ischemia lasted 45 min. After 48-hour reperfusion, we observed significantly improved renal function parameters, reduced apoptotic index and neutrophil/macrophage infiltration in kidney parenchyma, and lower expression of tubular damage markers and pro-inflammatory cytokines in MSCD − 7 in comparison to MSCD + 1 and saline control groups. Next, comparative high-throughput RNA sequencing of MSCD − 7 vs. SD − 7 non-ischemic right kidneys highlighted significant down-regulation of fatty acid biosynthesis and up-regulation of PPAR-α pathway. Such a preferential regulation towards lipid catabolism was associated with decreased levels of lipid peroxidation products, i.e. malondialdehyde and 4-hydroxy-2-nonenal, in MSCD − 7 versus SD − 7 ischemic kidneys. Our findings suggest that MSC pretreatment may exert protective effects against renal I/R by modulating lipid metabolism in rats.

Correlation between Nicotinamide Phosphoribosyl Transferase(NAMPT) level andclinicopathological criteria in colorectal cancer patients

Background:Colorectal cancer (CRC) is one of the most common cancers worldwide, with the highest incidence rates western countriesThe 5-year survival rate for a patient diagnosed with stage I or II colorectal cancer, is up to 90%. However, the 5-year survival rate for patients diagnosed with stage IV disease, once the cancer has metastasized to other organs, is only 12%. Aim of the work :is todetect levels of Visfatin,Nitric oxide,Lipid peroxide and Superoxide dismutase in serum of patients with colorectal cancer and compare results with patients with benign colorectal tumor and with control group and detect the relation of each of them to the clinic-pathological criteria colorectal cancer. Patients and methods:This study was performed at Sohag University Hospital from December 2015 to June 2016, eighty-five persons were enrolled the study and divided into three groups. 60 patients with colorectal cancer, 10 patients with begin colorectal tumors all of them were selected from SohagCancer Institute and Sohag University Hospital and 15 healthy persons of matched age and sex without evidence of any cancer (controls). All were matched for age and sex, for each participantcomplete medical history, physical examination, and routine investigations were done.Nicotinamidephosphoribosyltransferase (NAMPT) was measured by Eliza kitsNitric oxide and Superoxide dismutase (SOD) activities level were measured by colorimetry.. Results:The serum levels of visfatinNAMPT,NO and lipid peroxidation products as MDAin patients with benign tumor were significantly higher than healthy controls ,in patients with colorectal cancer the levels is significantly higher than healthy controls and patients with benign tumor (p-value < 0.001), and there is significant relations between levels of NAMPT and the clinicopathologicalcritiria of the cancer ,In contrast the levels of antioxidant enzyme (superoxide dismutase) where altereddecreased in colorectal cancer group , benign lesions group comparing to healthy control group . Conculsion:our study relieved that there is positive relation between level of visfatin and colorectal caneroccurance and cancer clinicopathological criteria . Also our study relievedColorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer.

Abstract 5425: The role of six transmembrane epithelial antigen of the prostate 2 in hepatocellular carcinoma

Abstract Introduction: The incidence of hepatocellular carcinoma (HCC) in Hispanics is three times higher than non-Hispanic whites, and even higher in South Texas (STX) Hispanics. This is attributed to a higher prevalence of hepatitis C, diabetes, obesity and perhaps genetic and epigenetic alterations. Knowledge regarding genetic alterations in Hispanics is sparse as demonstrated by the lack of Hispanics with HCC in The Cancer Genome Atlas (TCGA). Therefore, our group sequenced paired adjacent liver and HCC tumor samples from STX Hispanics, which highlighted a gene over-expressed in tumors of Hispanics, called the Six Transmembrane Epithelial Antigen of the Prostate 2 (STEAP2). STEAP2 is a metalloreductase of iron and copper and is implicated in increased iron and reactive oxygen species in the liver which can lead to the progression of inflammation and cirrhosis. STEAP2 may play an important oncogenic role in HCC, especially in the setting of obesity. We propose to test the hypothesis that overexpression of STEAP2 will lead to malignant property in HCC cells resulting in enhanced proliferation, survival, invasiveness, and eventually development of HCC, especially in obese hosts. Methods: Hispanic paired tissue continues to be collected from our institution for RNA sequencing and establishment of Hispanic HCC cell lines. STEAP2 RNA and protein expression levels in Hispanic paired samples versus Caucasian paired samples were evaluated by RT-PCR, Western blot, and immunohistochemistry. Knockdown and overexpression of STEAP2 were established in HCC cell lines and in primary Hispanic HCC cell lines to examine the effects on iron levels, oxidative stress, proliferation, invasiveness, apoptosis and cell cycle in vitro. Results: Hispanic HCC RNA sequencing data compared to TCGA HCC RNA sequencing data (no Hispanics) demonstrated the overexpression of STEAP2 in HCC tumors in Hispanic patients, which were validated by RT-PCR data and Western blot data. Lipid peroxidation product, 4-hydroxynonenal, and copper levels were higher in HCC tumor versus adjacent tissue. Iron levels were higher in adjacent tissue versus tumor tissue in Hispanics. Knockdown of STEAP2 in SNU398 cells decreased proliferation and migration, while in HUH7 cells STEAP2 knockdown only decreased migration. Conclusions: STEAP2 is specifically overexpressed in HCC tumors in Hispanics in comparison to HCC tumors in non-Hispanic whites and appears to play a malignant-promoting role in HCC cells. Further studies to establish the role of STEAP2 as a tumor promoter in HCC and the mechanisms by which it promotes carcinogenesis are underway. The proposed studies will likely yield mechanistic insights into the molecular mechanisms that drive HCC development and progression in South Texas Hispanics and potential therapeutic targets involving STEAP2-mediated metal ion metabolism and oxidative stress. Citation Format: Carla R. Zeballos, Hakim Bouamar, Xiang Gu, Yidong Chen, Francisco G. Cigarroa, LuZhe Sun. The role of six transmembrane epithelial antigen of the prostate 2 in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5425. doi:10.1158/1538-7445.AM2017-5425

ДОКАЗАТЕЛЬСТВА ЭФФЕКТИВНОСТИ И ФУНКЦИОНАЛЬНОЙ НАПРАВЛЕННОСТИ СПЕЦИАЛИЗИРОВАННОГО ПРОДУКТА В КЛИНИЧЕСКИХ ИСПЫТАНИЯХ

Aim. To perform clinical trials aimed to test effectiveness and functional properties of Energiya biologically active additive (BAA) in people exposed to high psychophysiological loads. Materials and Methods. We conducted clinical trials of new formula of Energiya BAA which contains (mg per 1 tablet): peach leaf (extract) – 100; Rhodiola quadrifida (extract) – 75; zinc asparaginate – 45.5; zinc – 8.5; cystine – 30; ascorbic acid – 25; quercetin – 10; rutin – 10; grape seed (extract) – 5; copper asparaginate – 4.4; copper – 0.7; sodium selenite – 0.11; selenium - 0,05; cifrol-5 (antioxidant complex) – 200. Thirty five volunteers were recruited as participants among people regularly exposed to increased psychophysiological loads: physicians, nurses, teachers, and long-haul drivers. Subjects' diet was supplemented with two tablets of the specialized product per day. The control group comprising 35 participants of similar occupations did not receive any bioactive additives. Levels of lipid peroxidation products and free radical activity were assessed based on malondialdehyde concentration. Microcirculatory vascular disturbances were estimated by rheoencephalography. Quality of life was evaluated in accordance with a factor determining health-related restrictions of physical loads; patient-reported data were also used. Results. It was established that supplementing the volunteers' diet with specialized product reduced the levels of lipid peroxidation products and, thus, reversed the symptoms of microcirculatory disturbances with a simultaneous improvement of quality of life, which could be associated with stabilization of cell membranes and energy metabolism, prevention of oxygen deficiency, and elimination of unfavorable oxidative processes. In the control group such positive changes were not observed. Conclusion. Using BAA Energia as a dietary factor normalizes the microcirculatory function, contributes to overall rehabilitation, and improves the quality of life affected by high psychophysiological loads.

Abstract 389: The Role of Amadori-Glycation in High Density Lipoprotein Dysfunction and Oxidative Stress in Patients With Diabetes

Objectives: Diabetes is associated with HDL dysfunction and oxidative stress. We recently demonstrated that HDL from patients with T2D has reduced anti-oxidant activity and it is pro-inflammatory. Here we used the 2 H 2 O-based metabolic labeling approach to test the hypothesis that hyperglycemia-induced glycation contributes to HDL dysfunction and oxidative stress in diet-controlled patients with T2D. Methods: HDL from patients with T2D and age- and BMI-matched healthy controls (n=7/group) was isolated and it’s anti-oxidant and cholesterol efflux properties were quantified. ApoAI cross-linking and HDL particle size distribution were anlyzed. HDL proteome composition and post-translational modification of proteins were quantified by shot-gun proteomics aproach. Metabolic 2 H 2 O-labeling coupled with high resolution mass spectrometry was applied to quantify HDL turnover and HDL proteome dynamics. Results: Despite significant differences in fasting blood glucose, insulin, insulin resistance and HbA1c, patients with T2D and controls had similar lipid (triglycerides, total cholesterol, and HDL cholesterol) and lipoprotein (apoAI and apoB100) profile. HDL from patients with T2D displayed increased levels of cross-linked apoAI and lipid-poor pre-β1 HDL partcicles. ApoB-depleted serum from T2D patients had reduced PON1 activity and macrophage-cholesterol efflux capacity, and increased levels of lipid peroxidation products measured as TBARS (all P&lt;0.05 ). HDL from patients with T2D was enriched with Amadori glycated apoAI and transferrin (Tf), the key HDL proteins involved in cholesterol and iron transport. The extent of glycations were associated with increased degradation of apoAI and Tf. ApoAI glycation was inversely correlated with ABCA1-induced cholesterol efflux activity of HDL (r=-0.52, P&lt;0.005), while Tf glycation had positive association with the TBARS levels (r=0.40, P&lt;0.05). Our in vivo HDL flux study demonstrated that glycated apoAI and Tf species were degraded 3 and 10 fold faster than the respective non-modified native proteins. Conclusions: HDL dysfunction and oxidative stress in T2D is related to glycation-induced instability of HDL proteins, including apoAI and Tf.

Improvement of Antioxidant Defences and Mood Status by Oral GABA Tea Administration in a Mouse Model of Post-Stroke Depression.

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD.