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

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.

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The effect of deoxynivalenol on hepatic cell line HepG2

Biotechnology in Animal Husbandry ◽

10.2298/bah0701583d ◽

2007 ◽

Vol 23 (5-6-1) ◽

pp. 583-588 ◽

Cited By ~ 6

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.

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

BioMetals ◽

10.1007/s10534-011-9453-2 ◽

2011 ◽

Vol 24 (5) ◽

pp. 951-958 ◽

Cited By ~ 6

Author(s):

Pablo Hernández-Franco ◽

Martín Silva ◽

Mahara Valverde ◽

Emilio Rojas

Keyword(s):

Oxidative Stress ◽

Cell Line ◽

Hepatic Cell ◽

Low Doses ◽

Hepatic Cell Line

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

Current Bioactive Compounds ◽

10.2174/1573407214666180226124526 ◽

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.

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