The cytoprotective effect of Trolox demonstrated with three types of human cells

1990 ◽  
Vol 68 (10) ◽  
pp. 1189-1194 ◽  
Author(s):  
Tai-Wing Wu ◽  
Noriaki Hashimoto ◽  
Jun Wu ◽  
Doug Carey ◽  
Ren-Ke Li ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Ventricular Myocytes ◽  
Sodium Dodecyl ◽  
Optimal Level ◽  
Human Cells ◽  
Water Soluble ◽  
Peroxyl Radicals ◽  
Azo Initiator ◽  
Dose Dependent ◽  
In Cells

Trolox, a hydrophilic analogue of α-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocytes against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2′-azo-bis(2-amidinopropane) HCl. Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes.Key words: oxyradicals, cytoprotection, hepatocytes, myocytes, erythrocytes.

Purpurogallin protects both ventricular myocytes and aortic endothelial cells of rats against oxyradical damage

1992 ◽  
Vol 70 (9) ◽  
pp. 803-809 ◽  
Author(s):  
Tai-Wing Wu ◽  
Jun Wu ◽  
Doug Carey ◽  
Ling-Hua Zeng
Keyword(s):  
Endothelial Cells ◽  
Xanthine Oxidase ◽  
Ventricular Myocytes ◽  
Cell Damage ◽  
Dependent Manner ◽  
Aortic Endothelial Cells ◽  
Electron Microscopies ◽  
First Time ◽  
Dose Dependent ◽  
Aortic Endothelial

Rat ventricular myocytes have been isolated and cultured by two separate procedures. Using phase-contrast and electron microscopies, we illustrate that (a) definitive cell damage is produced when myocytes are exposed to xanthine oxidase – hypoxanthine and (b) purpurogallin between 0.25 and 1.0 mM prolongs survival of both myocyte preparations in a dose-dependent manner. The cytoprotection produced by 1 mM purpurogallin exceeds that given by 2 mM each of ascorbate, Trolox, and mannitol, or 24 200 IU superoxide dismutase/L and (or) 92 000 IU catalase/L. Furthermore, we noted, for the first time, that purpurogallin markedly protects rat aortic endothelial cells, a key target of free radical generation and attack. In contrast, Trolox has a negligible effect here. Mechanistically, we showed that purpurogallin inhibits urate formation by xanthine oxidase more potently than allopurinol. Also, the compound diminishes formation of superoxide-reduced cytochrome c. Therefore, purpurogallin is a potent protector of ventricular myocytes and aortic endothelial cells, both of which are important cells in the cardiovascular system.Key words: purpurogallin, endothelial cells, myocytes.

scholarly journals Amphotericin B protects cis-parinaric acid against peroxyl radical-induced oxidation: amphotericin B as an antioxidant.

1997 ◽  
Vol 41 (4) ◽  
pp. 743-747 ◽  
Author(s):  
K Osaka ◽  
V B Ritov ◽  
J F Bernardo ◽  
R A Branch ◽  
V E Kagan
Keyword(s):  
Amphotericin B ◽  
Antioxidant Properties ◽  
Model System ◽  
Antioxidant Effect ◽  
Water Soluble ◽  
Peroxyl Radicals ◽  
Target Cells ◽  
Prooxidant Effect ◽  
Parinaric Acid ◽  
Azo Initiator

The antifungal effects of amphotericin B are believed to be due to two possibly interrelated mechanisms: an increase in permeation by binding to sterols in cellular membranes and a prooxidant effect causing oxidative damage in target cells. However, the seven conjugated double bonds in amphotericin B raise the possibility that it could be highly susceptible to autoxidation, causing an antioxidant effect. In the present study, we investigated the prooxidant and antioxidant properties of amphotericin B in a model system in which oxidation of a reporter molecule, cis-parinaric acid, was induced by azo initiators of peroxyl radicals. Since interactions of amphotericin B with sterols are essential for its pharmacological and toxic actions, we also studied the effects of cholesterol on the prooxidant and antioxidant properties of amphotericin B. Amphotericin B caused a noncollisional quenching of a characteristic fluorescence of cholesteryl cis-parinarate integrated in liposomes, suggesting the formation of amphotericin B-cholesteryl cis-parinarate complex. This effect of amphotericin B was ablated by increasing concentrations of cholesterol. We found that amphotericin B inhibited oxidation of cis-parinaric acid complexed with human serum albumin [using a water-soluble azo initiator, 2,2'-azobis(2aminopropane)dihydrochloride] and in liposomes [using a lipid-soluble azo initiator, 2,2'-azobis(2,4-dimethylvaleronitrile)]. The inhibitory effect of amphotericin B on 2,2'-azobis(2,4-dimethylvaleronitrile)-induced peroxidation of cis-parinaric acid in liposomes was also diminished by cholesterol. The antioxidant effect of amphotericin B in this model system suggests that amphotericin B does not exert its pharmacological and toxicological responses through a prooxidant effect to cause damage in target cells.

Benzophenone-photosensitized autoxidation of linoleate in solution and sodium dodecyl sulfate micelles

1987 ◽  
Vol 65 (11) ◽  
pp. 2529-2540 ◽  
Author(s):  
Lawrence Ross Coates Barclay ◽  
Kimberly Ann Baskin ◽  
Steven Jeffrey Locke ◽  
Tanya Diane Schaefer
Keyword(s):  
Linoleic Acid ◽  
Rate Constants ◽  
Sodium Dodecyl ◽  
Kinetic Studies ◽  
Water Soluble ◽  
Peroxyl Radicals ◽  
Phenolic Antioxidants ◽  
Radical Chain ◽  
Geometrical Isomers ◽  
Chain Reactions

Diffusion studies show that benzophenone (BP), linoleic acid, and methyl linoleate partition completely into the micelles of phosphate buffer/0.10 M SDS. Water-soluble compounds 4-sulphomethylbenzophenone, sodium salt (BP−), azobis(2-amidinopropane•HCl) (ABAP) and 2,5,7,8-tetramethyl-6-hydroxychroman-2-carboxylate (Trolox) show partial partitioning into the micelles. BP- and BP−-photosensitized oxidation of linoleic acid in 0.50 M SDS exhibited characteristics of free radical chain reactions including: (1) inhibition by phenolic antioxidants, (2) no retardation by singlet oxygen quenchers, and (3) the formation of conjugated hydroperoxides with cis,trans to trans,trans ratios of geometrical isomers typical of autoxidation. Quantitative kinetic studies of the order in substrate, RH, and the rate of chain initiation, Ri, show that the classical rate law, −d[O2]/dt = kp/2kt1/2[RH]Ri1/2 applies to BP-photoinitiated autoxidation of linoleic acid in SDS and the oxidizability (kp/2kt1/2 = 4.42 × 10−2 M−1/2 s−1/2) is the same as that found with a thermal initiator. The rotating sector method gave absolute rate constants for linoleic acid autoxidation in 0.50 M SDS for propagation (kp = 36.2 M−1 s−1) and termination (2kt = 3.52 × 105 M−1 s−1), significantly lower than values in polar organic solvents; attributed to solvation of polar peroxyls in aqueous SDS. Depressed inhibition rate constants (kinh) for α-tocopherol, Trolox, and pentamefhylhydroxychroman (PMHC) in 0.50 M SDS compared to kinh in tert-butyl alcohol are attributed to hydrogen bonding effects on the peroxyl radicals and on the inhibitors.

Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

2018 ◽  
Vol 11 (4) ◽  
pp. 4162-4169
Author(s):  
Mayank Kulshreshtha ◽  
Manjul Pratap Singh
Keyword(s):  
Skin Diseases ◽  
Scientific Data ◽  
Water Soluble ◽  
Histopathological Analysis ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Biochemical Studies ◽  
Pharmacological Potential ◽  
Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

scholarly journals Role of leukemia inhibitor factor (LIF) in decidualisation of murine uterine stromal cells in vitro

2004 ◽  
Vol 181 (3) ◽  
pp. 477-492 ◽  
Author(s):  
AA Fouladi Nashta ◽  
CV Andreu ◽  
N Nijjar ◽  
JK Heath ◽  
SJ Kimber
Keyword(s):  
In Vitro Culture ◽  
Stromal Cells ◽  
Control Level ◽  
Calf Serum ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Alp Activity ◽  
Dose Dependent ◽  
In Cells

Decidualisation of uterine stromal cells is a prerequisite for implantation of the embryo in mice. Here we have used an in vitro culture system in which stromal cells decidualise as indicated by a number of markers, including an increase in alkaline phosphatase (ALP) activity. The latter was used as a quantitative marker of decidualisation in the presence of low (2%) fetal calf serum. Prostaglandin E(2) (PGE(2)), which is known to induce decidualisation, increased ALP activity, and this effect was blocked in a dose-dependent manner by indomethacin. Leukemia inhibitory factor (LIF) was then examined, but it had no effect on PGE(2) secretion. However, LIF suppressed ALP activity in a dose-dependent manner in the presence of 2% serum, while an inhibitor of LIF that competes for binding to its receptor reversed the effect of LIF and increased ALP activity above the control level. In serum-free cultures, stromal cells differentiated rapidly, and no differences were observed between LIF-treated and untreated cultures. Stromal cells produce LIF during in vitro culture, and this peaked at 48 h. Freshly collected stromal cells from both day-2 and -4 pregnant mice expressed mRNA for the LIF receptor, and the transcript level was higher in cells isolated on day 4. However, no differences were observed in the relative levels of transcripts in cells from day 2 and day 4 after culture, nor were there differences between the LIF-treated cultures and controls. Therefore, in this study, we have shown that LIF suppresses decidualisation of murine uterine stromal cells in the presence of serum, this is not due to the regulation of PGE(2) secretion by stromal cells.

scholarly journals Synthesis of a thermoresponsive crosslinked MEO2MA polymer coating on microclusters of iron oxide nanoparticles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alejandro Lapresta-Fernández ◽  
Alfonso Salinas-Castillo ◽  
Luis Fermín Capitán-Vallvey
Keyword(s):  
Iron Oxide ◽  
Synthesis Temperature ◽  
Water Soluble ◽  
Covalent Attachment ◽  
Solution Temperature ◽  
Tetraethylene Glycol ◽  
Critical Solution Temperature ◽  
Large Size ◽  
Transmission Electron ◽  
Azo Initiator

AbstractEncapsulation of magnetic nanoparticles (MNPs) of iron (II, III) oxide (Fe3O4) with a thermopolymeric shell of a crosslinked poly(2-(2-methoxyethoxy)ethyl methacrylate) P(MEO2MA) is successfully developed. Magnetic aggregates of large size, around 150–200 nm are obtained during the functionalization of the iron oxide NPs with vinyl groups by using 3-butenoic acid in the presence of a water soluble azo-initiator and a surfactant, at 70 °C. These polymerizable groups provide a covalent attachment of the P(MEO2MA) shell on the surface of the MNPs while a crosslinked network is achieved by including tetraethylene glycol dimethacrylate in the precipitation polymerization synthesis. Temperature control is used to modulate the swelling-to-collapse transition volume until a maximum of around 21:1 ratio between the expanded: shrunk states (from 364 to 144 nm in diameter) between 9 and 49 °C. The hybrid Fe3O4@P(MEO2MA) microgel exhibits a lower critical solution temperature of 21.9 °C below the corresponding value for P(MEO2MA) (bulk, 26 °C). The MEO2MA coating performance in the hybrid microgel is characterized by dynamic light scattering and transmission electron microscopy. The content of preformed MNPs [up to 30.2 (wt%) vs. microgel] was established by thermogravimetric analysis while magnetic properties by vibrating sample magnetometry.

Purpurogallin is a more powerful protector of kidney cells than Trolox and allopurinol

1992 ◽  
Vol 70 (8) ◽  
pp. 684-690 ◽  
Author(s):  
Ling-Hua Zeng ◽  
Tai-Wing Wu
Keyword(s):  
Xanthine Oxidase ◽  
Phase Contrast ◽  
Potent Inhibitor ◽  
Rat Kidney ◽  
Peroxyl Radicals ◽  
Kidney Cells ◽  
Tubular Epithelial Cells ◽  
Electron Microscopic ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition

Phase contrast and electron microscopic experiments demonstrated that oxyradicals generated with xanthine oxidase and hypoxanthine markedly damage rat kidney mesangial and porcine tubular epithelial cells. Purpurogallin, a phenol found in oak nutgalls, prolongs survival of the xanthine oxidase exposed renal cells three- to nine-fold longer than those without purpurogallin present. At levels equimolar to purpurogallin, either Trolox or allopurinol is less effective in delaying cell necrosis. Purpurogallin scavenges not only xanthine oxidase generated oxyradicals, but also non-enzymatically produced peroxyl radicals, more actively than equimolar levels of Trolox or allopurinol. Purpurogallin inhibits xanthine oxidase with severalfold higher potency than allopurinol and its more active metabolite oxypurinol. Therefore, purpurogallin is a stronger antioxidant than Trolox and a more potent inhibitor of xanthine oxidase than allopurinol as well as oxypurinol.Key words: purpurogallin, kidney cells, oxyradical damage, xanthine oxidase inhibition, antioxidant.

scholarly journals Enzymatic identification of the load-bearing boundary lubricant in the joint.

Rheumatology ◽  
1998 ◽  
Vol 37 (2) ◽  
pp. 137-142 ◽  
Author(s):  
B A Hills ◽  
M K Monds
Keyword(s):  
Water Soluble ◽  
Surprising Result ◽  
Lubrication System ◽  
Load Bearing ◽  
Bovine Articular Cartilage ◽  
Boundary Lubricant ◽  
Surface Active ◽  
Per Se ◽  
Dose Dependent ◽  
Wear Tests

Abstract Bovine articular cartilage and synovial fluid (SF) were co-incubated with one of three enzymes selected to destroy each of the three major contenders for the active ingredient imparting such remarkable load-bearing lubrication to the normal joint. Destroying hyaluronic acid (HA), alias hyaluronan, with hyaluronidase, both frictional and wear tests displayed no significant change in accordance with most previous studies of SF alone. Destroying surface-active phospholipid (SAPL) with phospholipase A2, there was a highly significant dose-dependent compromise of lubrication as recorded on both tests. Trypsin produced a somewhat surprising result in that lubrication of the cartilage actually improved. This result can be interpreted as indicating that lubricin is not the lubricant per se, but, as a water-soluble, macromolecular, proteinaceous carrier for phospholipid, its destruction caused more SAPL to be deposited as the true load-bearing lubricant. These results are discussed in the context that SAPL, lubricin and HA each have specific roles in a comprehensive lubrication system.

scholarly journals Interaction of autoantibodies to thyrotropin receptor with a hydrophilic subunit of the thyrotropin receptor

1985 ◽  
Vol 228 (1) ◽  
pp. 111-117 ◽  
Author(s):  
E Davies Jones ◽  
F A Hashim ◽  
Y Kajita ◽  
F M Creagh ◽  
P R Buckland ◽  
...  
Keyword(s):  
Gradient Centrifugation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Water Soluble ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Thyrotropin Receptor ◽  
Freezing And Thawing ◽  
Sucrose Density Gradient Centrifugation ◽  
A Subunit

Reduction of human thyroid membranes with dithiothreitol caused the release of a water-soluble glycoprotein which neutralized the thyrotropin (TSH) receptor-binding and thyroid-stimulating activities of Graves‘ serum. Analysis of the protein by gel filtration and sucrose density gradient centrifugation allowed estimates of 3.45 nm for the Stokes’ radius, 3.6 S for the s20,w and 47 000 +/- 5000 (mean +/- S.D.; n = 4) for the Mr. The material released by dithiothreitol treatment could be crosslinked to 125I-labelled TSH coupled to N-hydroxysuccinimidyl 4-azidobenzoate (125I-HSAB-TSH), suggesting that it contained a component of the TSH receptor. Furthermore, analysis of the crosslinked material by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis indicated that it contained the TSH receptor A subunit (Mr 50 000). Several factors suggested therefore that the glycoprotein released by dithiothreitol treatment of human thyroid membranes was the TSH receptor A subunit. In particular, (a) both preparations were hydrophilic and were released from membranes by reduction, (b) they had similar Mr values and (c) both preparations crosslinked to 125I-HSAB-TSH. Material similar to the TSH receptor A subunit was released from thyroid membranes by treatment with papain, probably as a result of cleavage of the receptor A subunit at a site close to the interchain disulphide bridge. A similar mechanism, involving thyroid proteinases, was probably involved in release of material with similar properties to the TSH receptor A subunit during freezing and thawing of human thyroid homogenates.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

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