scholarly journals Selenium deficiency as a model of experimental pre-eclampsia in rats

Reproduction ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 635-641 ◽  
Author(s):  
J Vanderlelie ◽  
K Venardos ◽  
A V Perkins
Keyword(s):  
Glutathione Peroxidase ◽  
Complex Disease ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Lipid Peroxides ◽  
Epidemiological Studies ◽  
Protein Carbonyls ◽  
Pregnant Rats ◽  
High Selenium

Epidemiological studies andin vitroanalysis demonstrate correlations between selenium status and human pre-eclampsia (PET). Selenium is an essential component in the anti-oxidant proteins glutathione peroxidase and thioredoxin reductase, which are produced in lower amounts in pre-eclamptic placenta. This study examined the effect of modulating dietary selenium content in pregnant rats. Rats were fed diets containing no selenium, 239 μg/kg selenium or 1000 μg/kg selenium, four weeks prior to and following conception. Significant pregnancy-specific increases in systolic blood pressure (116.4 ± 5.2 mmHg vs 108 ± 6.8 mmHg vs 111.4 ± 4.7 mmHg) and proteinuria (9.68 ± 2.12 μg/ml vs 5.93 ± 1.59 μg/ml vs 4.43 ± 0.96 μg/ml) were demonstrated in animals fed a selenium free-diet when compared with normal or high selenium diets. Placental weight and pup number were not affected by selenium deprivation, however a significant decrease in the pup weight was evident. Selenium deprivation caused dose-dependent decreases in liver glutathione peroxidase (28.55 ± 3.82 mmoles/min/mg vs 34.68 ± 8.64 mmoles/min/mg) and thioredoxin reductase (2.37 ± 1.25 U/mg vs 6.68 ± 1.82 U/mg) activity, whereas superoxide dismutase activity remained constant. Placental activity of these enzymes also decreased leading to oxidative stress as measured by increased lipid peroxides (17.92 ± 1.78 μmoles/mg vs 8.30 ± 5.52 μmoles/mg) and protein carbonyls in tissue extracts from selenium-free animals. These results suggest that selenium deficiency in pregnant rats leads to symptoms similar to those seen in human PET and may provide an experimental model for studying this complex disease.

scholarly journals ANTIOXIDANT PROPERTIES OF SINAPIC ACID: IN VITRO AND IN VIVO APPROACH

2017 ◽  
Vol 10 (6) ◽  
pp. 255 ◽  
Author(s):  
Nithya R ◽  
Subramanian S
Keyword(s):  
Antioxidant Properties ◽  
Intraperitoneal Administration ◽  
Radical Scavenging ◽  
Sinapic Acid ◽  
Lipid Peroxides ◽  
Diabetic Rats ◽  
Antioxidant Potential ◽  
Protein Carbonyls

Objective: This study was aimed to evaluate the antioxidant potential of sinapic acid in both in vitro and in vivo. Recently, we have reported that oral administration of sinapic acid (3,5-dimethoxy 4-hydroxycinnamic acid) an active phyto ingredient widely distributed in rye, mustard, berries, and vegetables has been shown to ameliorate hyperglycemia.Methods: Experimental Type 2 diabetes was induced in male Wistar rats by feeding high-fat diet to induce insulin resistance followed by intraperitoneal administration of a single low dose streptozotocin (35 mg/kg body weight [bw]). Sinapic acid was administered orally at a concentration of 25 mg/kg bw/rat/day for 30 days, and its efficacy was compared with metformin. In vitro, antioxidant scavenging properties of sinapic acid were determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), superoxide, and nitric oxide (NO) assay.Results: Sinapic acid treatment showed a significant decline in the levels of lipid peroxides, hydroperoxides and protein carbonyls in the plasma and vital tissues of diabetic rats. The treatment also improved the antioxidant status in diabetic rats indicating the antioxidant potential of sinapic acid. In addition, the results of DPPH, ABTS, superoxide, and NO radical scavenging assays substantiate the free radical scavenging efficacy of sinapic acid.Conclusion: The results of this study evidenced that sinapic acid possess significant antioxidant properties which in turn may be responsible for its antidiabetic properties.

Effects of a selenium deficient diet on thyroid function of normal and perchlorate treated rats

1988 ◽  
Vol 118 (4) ◽  
pp. 495-502 ◽  
Author(s):  
J. Golstein ◽  
B. Corvilain ◽  
F. Lamy ◽  
D. Paquer ◽  
J. E. Dumont
Keyword(s):  
Thyroid Hormone ◽  
Tap Water ◽  
Selenium Deficiency ◽  
Thyroid Peroxidase ◽  
Deficient Diet ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis

Abstract. Pregnant rats were submitted to a selenium-deficient diet immediately after mating; it was continued for 4 weeks after delivery. The pups were sacrificed at 3 and 4 weeks of age. Perchlorate, an antithyroid agent inhibiting iodide trapping in the thyroid, was administered via the drinking water to half of the rats. Rats submitted to a normal laboratory diet and to the experimental diet supplemented with selenium were used as controls. The effects of selenium deficiency were an increase in the number of growth abnormalities, growth retardation, and decreased seleno-dependent glutathione peroxidase (GSH-Px) activity in plasma and in various organs. These effects were relieved by selenium supplementation in the diet. Perchlorate treatment induced the classic picture of primary hypothyroidism. Selenium deficiency increased thyroid hormone levels in perchlorate-treated rats and in controls drinking tap water. In the latter group, it also decreased TSH plasma concentration and thyroid weight. These effects were partially reversed by Se supplementation. In vitro experiments, performed on adult rats, revealed increased radioiodide uptake and organification in glands from the rats submitted to the selenium-free diet. Plasma T3 half-life was similar in control and Se-deficient rats. These data suggest a higher efficiency of thyroid hormone synthesis in the thyroids of selenium-deficient rats, despite a lower thyroid stimulation as evaluated by serum TSH. They are compatible with the hypothesis that decreased selenium supply, leading to a decreased GSH-Px in the thyroid, increases hydrogen peroxide steady state level and thus thyroid peroxidase activity and thyroid hormone synthesis.

scholarly journals Effects of Dietary Selenium Deficiency or Excess on Selenoprotein Gene Expression in the Spleen Tissue of Pigs

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1122 ◽  
Author(s):  
Zhuang Lu ◽  
Pengzu Wang ◽  
Teng Teng ◽  
Baoming Shi ◽  
Anshan Shan ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Thioredoxin Reductase ◽  
Selenium Deficiency ◽  
Type I ◽  
Mrna Levels ◽  
Spleen Tissue ◽  
Selenoprotein K ◽  
Selenoprotein Genes ◽  
Se Deficiency ◽  
Selenoprotein M

To evaluate the effects of dietary Se deficiency and excess on the mRNA levels of selenoproteins in pig spleen tissues, 20 healthy uncastrated boars (Duroc × Landrace × Yorkshire, 10 ± 0.72 kg) were randomly divided into four groups (5 pigs per group). The pigs were fed a Se deficient corn-soybean basal feed (Se content <0.03 mg/kg) or basal feed with added sodium selenite at 0.3, 1.0, or 3.0 mg Se/kg diet, respectively. The experiment lasted 16 weeks. The spleen tissue was collected to examine the mRNA expression levels of 24 selenoprotein genes at the end of the study. Compared with pigs in other groups, those fed with the 1.0 mg Se/kg diet had higher mRNA levels of glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), deiodinase type II (Dio2), thioredoxin reductase 3 (Txnrd3), selenoprotein H (Selh), selenoprotein N, 1 (Sepn1), selenoprotein P1 (Sepp1), and selenoprotein V (Selv) in the spleen (p < 0.05). Dietary Se deficiency resulted in lower mRNA levels of Gpx1, Gpx2, glutathione peroxidase 3 (Gpx3), Dio2, thioredoxin reductase 2 (Txnrd2), Txnrd3, Selh, selenoprotein I (Seli), selenoprotein K (Selk), selenoprotein M (Selm), Sepn1, Sepp1, and Selv in the spleen than the other three groups. Dietary Se levels did not affect the mRNA levels of glutathione peroxidase 4 (Gpx4), deiodinase type I (Dio1), deiodinase type III (Dio3), selenophosphate synthetase 2 (Sephs2), thioredoxin reductase 1 (Txnrd1), selenoprotein O (Selo), selenoprotein S (Sels), selenoprotein W (Selw), selenoprotein X (Selx), and selenoprotein 15 (Sel15) in the spleen (p > 0.05). Dietary Se levels can affect the transcription levels of 14 selenoprotein genes in the spleen of pigs.

scholarly journals Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells

2010 ◽  
Vol 298 (5) ◽  
pp. F1244-F1253 ◽  
Author(s):  
Gary E. Olson ◽  
John C. Whitin ◽  
Kristina E. Hill ◽  
Virginia P. Winfrey ◽  
Amy K. Motley ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Specific Binding ◽  
Selenium Deficiency ◽  
Basement Membranes ◽  
Whole Body ◽  
Kidney Cortex ◽  
Plasma Selenium ◽  
Tubule Cells

Glutathione peroxidase-3 (Gpx3), also known as plasma or extracellular glutathione peroxidase, is a selenoprotein secreted primarily by kidney proximal convoluted tubule cells. In this study Gpx3−/−mice have been produced and immunocytochemical techniques have been developed to investigate Gpx3 metabolism. Gpx3−/−mice maintained the same whole-body content and urinary excretion of selenium as did Gpx3+/+mice. They tolerated selenium deficiency without observable ill effects. The simultaneous knockout of Gpx3 and selenoprotein P revealed that these two selenoproteins account for >97% of plasma selenium. Immunocytochemistry experiments demonstrated that Gpx3 binds selectively, both in vivo and in vitro, to basement membranes of renal cortical proximal and distal convoluted tubules. Based on calculations using selenium content, the kidney pool of Gpx3 is over twice as large as the plasma pool. These data indicate that Gpx3 does not serve in the regulation of selenium metabolism. The specific binding of a large pool of Gpx3 to basement membranes in the kidney cortex strongly suggests a need for glutathione peroxidase activity in the cortical peritubular space.

scholarly journals Expression Silencing of Glutathione Peroxidase 4 in Mouse Erythroleukemia Cells Delays In Vitro Erythropoiesis

2021 ◽  
Vol 22 (15) ◽  
pp. 7795
Author(s):  
Marlena Rademacher ◽  
Hartmut Kuhn ◽  
Astrid Borchert
Keyword(s):  
Glutathione Peroxidase ◽  
Ex Vivo ◽  
Lipid Peroxides ◽  
Erythroid Differentiation ◽  
Conditional Knockout ◽  
Erythroleukemia Cells ◽  
Vitro Model ◽  
Mouse Erythroleukemia

Among the eight human glutathione peroxidase isoforms, glutathione peroxidase 4 (GPX4) is the only enzyme capable of reducing complex lipid peroxides to the corresponding alcohols. In mice, corruption of the Gpx4 gene leads to embryonic lethality and more detailed expression silencing studies have implicated the enzyme in several physiological processes (e.g., embryonal cerebrogenesis, neuronal function, male fertility). Experiments with conditional knockout mice, in which expression of the Gpx4 gene was silenced in erythroid precursors, indicated a role of Gpx4 in erythropoiesis. To test this hypothesis in a cellular in vitro model we transfected mouse erythroleukemia cells with a Gpx4 siRNA construct and followed the expression kinetics of erythropoietic gene products. Our data indicate that Gpx4 is expressed at high levels in mouse erythroleukemia cells and that expression silencing of the Gpx4 gene delays in vitro erythropoiesis. However, heterozygous expression of a catalytically inactive Gpx4 mutant (Gpx4+/Sec46Ala) did not induce a defective erythropoietic phenotype in different in vivo and ex vivo models. These data suggest that Gpx4 plays a role in erythroid differentiation of mouse erythroleukemia cells but that heterozygous expression of a catalytically inactive Gpx4 is not sufficient to compromise in vivo and ex vivo erythropoiesis.

scholarly journals Lactobacillus fermentum JX306 Restrain D-galactose-induced Oxidative Stress of Mice through its Antioxidant Activity

2020 ◽  
Vol 69 (2) ◽  
pp. 205-205 ◽  
Author(s):  
DI ZHANG ◽  
CHUANG LI ◽  
RUIRUI SHI ◽  
FENGCHUN ZHAO ◽  
ZHENGYOU YANG
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Thioredoxin Reductase ◽  
Probiotic Strain ◽  
Lactobacillus Fermentum ◽  
Transcriptional Level ◽  
Liver And Kidney ◽  
Hydrogen Radical ◽  
Lipid Peroxidation Inhibition

Oxidative stress-induced series of related degenerative diseases have received widespread attention. To screen new lactic acid bacteria (LAB) strains to resist oxidative stress, traditional Chinese fermented vegetables were used as a resource library to screen of LAB. The Lactobacillus fermentum JX306 strain, which showed high scavenging activity of DPPH free radical and hydrogen radical, and a strong lipid peroxidation inhibition rate in vitro was selected. L. fermentum JX306 was also examined for its antioxidant capacity in D-galactose-induced aging mice. The results showed that L. fermentum JX306 could significantly decrease malondialdehyde (MDA) levels and improve the activity of glutathione peroxidase (GSH-Px), and total antioxygenic capacity (TOC) in the serum, kidney, and liver. Meanwhile, the strain could remarkably upregulate the transcriptional level of the antioxidant-related enzyme genes, such as peroxiredoxin1 (Prdx1), glutathione reductase (Gsr), glutathione peroxidase (Gpx1), and thioredoxin reductase (TR3) encoding genes in the liver. Besides, histopathological observation proves that this probiotic strain could effectively inhibit oxidative damage to the liver and kidney in aging mice. Therefore, this unique antioxidant strain may have a high application value in the functional food industry and medicine industry.

Adverse Influence of Cigarette Smoking on the Endothelium

1993 ◽  
Vol 70 (04) ◽  
pp. 707-711 ◽  
Author(s):  
Andrew D Blann ◽  
Charles N McCollum
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Tobacco Smoke ◽  
Lipid Peroxides ◽  
Short Exposure ◽  
Acute Effects ◽  
Adverse Influence ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe effect of smoking on the blood vessel intima was examined by comparing indices of endothelial activity in serum from smokers with that from non-smokers. Serum from smokers contained higher levels of von Willebrand factor (p <0.01), the smoking markers cotinine (p <0.02) and thiocyanate (p <0.01), and was more cytotoxic to endothelial cells in vitro (p <0.02) than serum from non-smokers. The acute effects of smoking two unfiltered medium tar cigarettes was to briefly increase von Willebrand factor (p <0.001) and cytotoxicity of serum to endothelial cells in vitro (p <0.005), but lipid peroxides or thiocyanate were not increased by this short exposure to tobacco smoke. Although there were correlations between von Willebrand factor and smokers consumption of cigarettes (r = 0.28, p <0.02), number of years smoking (r = 0.41, p <0.001) and cotinine (r = 0.45, p <0.01), the tissue culture of endothelial cells with physiological levels of thiocyanate or nicotine suggested that these two smoking markers were not cytotoxic. They are therefore unlikely to be directly responsible for increased von Willebrand factor in the serum of smokers. We suggest that smoking exerts a deleterious influence on the endothelium and that the mechanism is complex.

Usefulness of collaboration between mathematical models and cell engineering for elucidating complex disease mechanisms and discover effective drugs

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Kohjitani ◽  
A Kashiwa ◽  
T Makiyama ◽  
F Toyoda ◽  
Y Yamamoto ◽  
...  
Keyword(s):  
Mathematical Model ◽  
In Silico ◽  
Complex Disease ◽  
Ion Selectivity ◽  
Public Institution ◽  
Cell Engineering ◽  
Funding Source ◽  
Patch Clamp Technique ◽  
In Silico Model

Abstract Background A missense mutation, CACNA1C-E1115K, located in the cardiac L-type calcium channel (LTCC), was recently reported to be associated with diverse arrhythmias. Several studies reported in-vivo and in-vitro modeling of this mutation, but actual mechanism and target drug of this disease has not been clarified due to its complex ion-mechanisms. Objective To reveal the mechanism of this diverse arrhythmogenic phenotype using combination of in-vitro and in-silico model. Methods and results Cell-Engineering Phase: We generated human induced pluripotent stem cell (hiPSC) from a patient carrying heterozygous CACNA1C-E1115K and differentiated into cardiomyocytes. Spontaneous APs were recorded from spontaneously beating single cardiomyocytes by using the perforated patch-clamp technique. Mathematical-Modeling Phase: We newly developed ICaL-mutation mathematical model, fitted into experimental data, including its impaired ion selectivity. Furthermore, we installed this mathematical model into hiPSC-CM simulation model. Collaboration Phase: Mutant in-silico model showed APD prolongation and frequent early afterdepolarization (EAD), which are same as in-vitro model. In-silico model revealed this EAD was mostly related to robust late-mode of sodium current occurred by Na+ overload and suggested that mexiletine is capable of reducing arrhythmia. Afterward, we applicated mexiletine onto hiPSC-CMs mutant model and found mexiletine suppress EADs. Conclusions Precise in-silico disease model can elucidate complicated ion currents and contribute predicting result of drug-testing. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists

scholarly journals Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Animal Studies ◽  
Citrus Fruit ◽  
Epidemiological Studies ◽  
Personal Health ◽  
Current Review ◽  
Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

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