scholarly journals Urate Oxidase Knockdown Decreases Oxidative Stress in a Murine Hepatic Cell Line

2009 ◽  
Vol 2 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Beth M. Cleveland ◽  
Stephen S. Leonard ◽  
Hillar Klandorf ◽  
Kenneth P. Blemings
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Cell Line ◽  
Antioxidant Defense System ◽  
Hepatic Cell ◽  
Urate Oxidase ◽  
Uric Acid Concentration ◽  
Wild Type ◽  
Hepatic Cell Line ◽  
Spin Resonance

Humans, birds, and some primates do not express the uric acid degrading enzyme urate oxidase (UOX) and, as a result, have plasma uric acid concentrations higher than UOX expressing animals. Although high uric acid concentrations are suggested to increase the antioxidant defense system and provide a health advantage to animals without UOX, knockout mice lacking UOX develop pathological complications including gout and kidney failure. As an alternative to the knockout model, RNA interference was used to decrease UOX expression using stable transfection in a mouse hepatic cell line (ATCC, FL83B). Urate oxidase mRNA was reduced 66% (p < 0.05) compared to wild type, as measured by real time RT-PCR. To determine if UOX knockdown resulted in enhanced protection against oxidative stress, cells were challenged with hexavalent chromium (Cr(VI)) or 3-morpholinosydnonimine hydrochloride (SIN-1). Compared to wild type, cells with UOX knockdown exhibited a 37.2 ± 3.5% reduction (p < 0.05) in the electron spin resonance (ESR) signal after being exposed to Cr(VI) and displayed less DNA fragmentation (p < 0.05) following SIN-1 treatment. Cell viability decreased in wild type cells (p < 0.05), but not cells with UOX knockdown, after treatment with SIN-1. These results are consistent with an increased intracellular uric acid concentration and an increased defense against oxidative stress.

Cu isotope fractionation response to oxidative stress in a hepatic cell line studied using multi-collector ICP-mass spectrometry

2018 ◽  
Vol 410 (9) ◽  
pp. 2385-2394 ◽  
Author(s):  
María R. Flórez ◽  
Marta Costas-Rodríguez ◽  
Charlotte Grootaert ◽  
John Van Camp ◽  
Frank Vanhaecke
Keyword(s):  
Oxidative Stress ◽  
Mass Spectrometry ◽  
Cell Line ◽  
Isotope Fractionation ◽  
Hepatic Cell ◽  
Hepatic Cell Line ◽  
Icp Mass Spectrometry ◽  
Cu Isotope

Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line

2010 ◽  
Vol 24 (3) ◽  
pp. 751-758 ◽  
Author(s):  
Yiyi Ye ◽  
Jianwen Liu ◽  
Jianhe Xu ◽  
Lijuan Sun ◽  
Mingcang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Hepatic Cell ◽  
Nano Sio2 ◽  
Hepatic Cell Line

scholarly journals The effect of deoxynivalenol on hepatic cell line HepG2

2007 ◽  
Vol 23 (5-6-1) ◽  
pp. 583-588 ◽  
Author(s):  
G. Dragomir ◽  
R. Huculeci ◽  
C. Munteanu ◽  
C. Ceapa ◽  
L. Bodea ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzyme ◽  
Cell Line ◽  
Hepg2 Cells ◽  
Hepatic Cell ◽  
Biochemical Effect ◽  
Hepatic Cell Line ◽  
Specific Activities

The biochemical effect of deoxynivalenol on HepG2 hepatocarcinom cells was examined at a concentration of 2.5 ?M and 24h of exposure. The antioxidant enzyme specific activities increased. Our results revealed that HepG2 cells exposed to this mycotoxin developed specific adaptative responses neutralizing oxidative stress.

Induction of oxidative stress by low doses of lead in human hepatic cell line WRL-68

BioMetals ◽  
2011 ◽  
Vol 24 (5) ◽  
pp. 951-958 ◽  
Author(s):  
Pablo Hernández-Franco ◽  
Martín Silva ◽  
Mahara Valverde ◽  
Emilio Rojas
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Hepatic Cell ◽  
Low Doses ◽  
Hepatic Cell Line

Synthesis, Characterization and In vitro Evaluation of N-Substituted- Sulfomoyl-Phenyl-Amino Carboxylic Acid Derivatives as Squalene Synthase Inhibitors

2019 ◽  
Vol 15 (4) ◽  
pp. 415-426
Author(s):  
Avani B. Chokshi ◽  
Mahesh T. Chhabria ◽  
Pritesh R. Desai
Keyword(s):  
Carboxylic Acid ◽  
Cell Line ◽  
Hepatic Cell ◽  
Squalene Synthase ◽  
Lipid Lowering ◽  
Assay Method ◽  
Aromatic Substituent ◽  
Hepatic Cell Line ◽  
Amino Carboxylic Acid

Background:Squalene Synthase is one of the cholesterol biosynthetic pathway enzymes, inhibition of which produces potent lipid lowering action. A variety of chemical classes have been evaluated for its inhibition to provide alternate antihyperlipidemic agents to statins.Methods:A series of N-substituted-sulfomoyl-phenyl-amino carboxylic acid derivatives were designed through pharmacophore modelling as Squalene Synthase inhibitors. We report here the synthesis, characterization and in vitro pharmacological screening of the designed molecules as Squalene synthase inhibitors. The target molecules were synthesized by a simple procedure and each molecule was characterized by IR, Mass, 1HNMR and 13CNMR spectroscopic techniques. As a primary site of action for cholesterol biosynthesis is liver, each of the molecules were first screened for in vitro cytotoxicity over human hepatic cell line (HepG2) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. The enzyme inhibition assay was performed on cell lysates prepared from HepG2 cells by Human Squalene Synthase ELISA kit, where test compounds were added in the nontoxic concentrations only.Results:Compound 5f was found to be most potent with the IC50 value of 11.91 µM. The CTC50 value for 5f on human hepatic cell line was > 1000 µM so it was considered that the compound was relatively safe and might be free of hepatotoxicity.Conclusion:From the results of our studies, it was observed that compounds with poly nuclear aromatic or hetero aromatic substituent on a side chain were more potent enzyme inhibitors and a distance of 4-5 atoms is optimum between amide nitrogen and hydroxyl group of carboxylic acid.

Phagocytic uptake and ROS-mediated cytotoxicity in human hepatic cell line of amphiphilic polyphosphazene nanoparticles

2012 ◽  
Vol 101A (1) ◽  
pp. 285-297 ◽  
Author(s):  
Liyan Qiu ◽  
Yue Chen ◽  
Menghua Gao ◽  
Cheng Zheng ◽  
Qinghe Zhao
Keyword(s):  
Cell Line ◽  
Hepatic Cell ◽  
Hepatic Cell Line ◽  
Phagocytic Uptake

Effect and Mechanism of Total Saponin of Dioscorea on Animal Experimental Hyperuricemia

2006 ◽  
Vol 34 (01) ◽  
pp. 77-85 ◽  
Author(s):  
Guang-Liang Chen ◽  
Wei Wei ◽  
Shu-Yun Xu
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Acid Concentration ◽  
Serum Uric Acid Level ◽  
Urate Oxidase ◽  
Uric Acid Concentration ◽  
Total Saponin ◽  
Test Kit ◽  
Serum Uric Acid Concentration ◽  
Potassium Oxonate

In this study, we investigated the effects and mechanisms of Total Saponin of Dioscorea (TSD) on animal experimental hyperuricemia. Mouse and rat hyperuricemic models were made by orally administering yeast extract paste once a day (30 and 20 g/kg, respectively), for 7 days. Yeast would disturb normal purine metabolism by increasing xanthine oxidase (XOD) activity and generating large quantities of uric acid. This model is similar to human hyperuricemia, which is induced by high-protein diets, due to a purine and nucleic acid metabolic disturbance. Another mouse hyperuricemia model was generated by intraperitoneal injection once with uric acid 250 mg/kg or potassium oxonate 300 mg/kg. Potassium oxonate, a urate oxidase inhibitor, can raise the serum uric acid level by inhibiting the decomposition of uric acid. Likewise, injecting uric acid can also increase serum uric acid concentration. The concentration of uric acid in serum or urine was detected by the phosphotungstic acid method, and the activity of XOD was assayed by a test kit. The results showed that TSD (240, 120 and 60 mg/kg, ig) could significantly lower the level of serum uric acid in hyperuricemic mice. TSD (120 and 60 mg/kg, ig) could also lower the level of serum uric acid in hyperuricemic rats, reduce the activity of XOD in the serum and liver of hyperuricemic rats, and increase the level of urine uric acid concentration as well as 24-hour total uric acid excretion. In conclusion, TSD possesses a potent anti-hyperuricemic effect on hyperuricemic animals, and the mechanism may be relevant in accelerating the excretion and decreasing the production of uric acid.

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