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At least 865 records · Page 48Linked to original sources
PubMed1993

Role of 2,3,5-trichlorophenyl methyl sulfone, a metabolite of 1,2,4-trichlorobenzene, in the induction of hepatic microsomal drug-metabolizing enzymes by 1,2,4-trichlorobenzene in rats.

2,3,5- and 2,4,5-trichlorophenyl methyl sulfides, 2,3,5- and 2,4,5-trichlorophenyl methyl sulfoxides, and 2,3,5- and 2,4,5-trichlorophenyl methyl sulfones (TCPSO2Mes) were detected in the urine of rats dosed with 1,2,4-trichlorobenzene (TCB). After the administration of 1,2,4-TCB to rats, swift decreases in concentrations of 1,2,4-TCB in blood, liver, kidneys, and adipose tissue were observed. On the other hand, 2,3,5-TCPSO2Me appeared in blood, liver, kidneys, and adipose tissue and remained detectable in the blood and the three tissues until 120 hr. The increases in the activities of aminopyrine N-demethylase and aniline hydroxylase and the contents of cytochromes P450 and b5 in hepatic microsomes produced by 1,2,4-TCB occurred after increases in the hepatic concentration of 2,3,5-TCSO2Me. 2,3,5- and 2,4,5-TCPSO2Me increased the above four parameters in rat liver microsomes. The inducing intensity of 2,3,5-TCPSO2Me was much higher than that of 2,4,5-TCPSO2Me. 2,3,5-TCPSO2Me was considered to be a potent inducer and to play a principal role in the induction by 1,2,4-TCB. When 1,2,4-TCB was injected ip into bile duct-cannulated rats, little 2,3,5-TCPSO2Me was detected in blood, liver, kidneys, and adipose tissue. In the antibiotic-pretreated rats dosed with 1,2,4-TCB, 2,3,5-TCPSO2Me concentrations in the blood and the three tissues markedly decreased. These findings suggest that the formation of methylsulfonyl metabolites from 1,2,4-TCB depends largely upon the metabolism of some precursor(s) excreted in the bile by intestinal microflora. The increasing effects of 1,2,4-TCB administration on the activities of aminopyrine- and aniline-metabolizing enzymes and the contents of cytochromes P450 and b5 in hepatic microsomes were not observed in the bile duct-cannulated rats. These findings provide evidence that the induction of drug-metabolizing enzymes by 1,2,4-TCB is not due to the action of 1,2,4-TCB itself but is due to its methylsulfonyl metabolite, 2,3,5-TCPSO2Me.

Animals↗
PubMed1994

Divinyl sulfone cross-linked hyperpolymeric human haemoglobin as an artificial oxygen carrier in anaesthetized spontaneously breathing rats.

The production of hyperpolymer haemoglobins, exhibiting sufficiently low colloid osmotic pressure and sufficiently low viscosity is possible, even in concentrations, and therewith oxygen transport capacity, high enough to supply an organism adequately with oxygen. Such hyperpolymers, when infused, are tolerated by anaesthetized rats in acute blood exchange experiments. Ex vivo determinations of plasma colloid osmotic pressure and both, plasma and whole blood kinematic viscosity during blood exchange showed, that corresponding properties found in vivo were refound within the animal. Furthermore we could show that hyperpolymers produced from desoxygenated human haemoglobin with divinyl sulfone as a crosslinker take part in tissue supply of oxygen to a substantial degree (about 50%) without and with increased inspiratory oxygen fraction, demonstrating the principal ability of hyperpolymers to transport oxygen in blood and to deliver it to tissues.

Animals↗
PubMed1985

Influence of phosphate, sulfonic, and sulfamic acids on sulfoconjugate release in the vascularly perfused mouse small intestine.

An in vitro vascularly and luminally perfused preparation of the murine small intestine was used to investigate the interference of isethionate, cyclamate and HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) with the luminal transport of the isoprenaline-sulfoconjugate as well as with the basolateral transport of naphthol-sulfoconjugate. The sulfonates and sulfamates when administered from the luminal as well as from the contraluminal side of the epithelium inhibited the transport of isoprenaline-sulfoconjugate. Inhibition of the naphthol-sulfoconjugate transport across the contraluminal epithelial membrane was less pronounced, but a countertransport phenomenon could be induced with cyclamate in the vascular medium. The presence of phosphate at the luminal side is essential for the transport of the isoprenaline-sulfoconjugate across the luminal membrane. This is not the case for bicarbonate. The conclusion is drawn that different transport systems for sulfoconjugates exist in the luminal and in the contraluminal membranes of the intestinal mucosa, which can be inhibited by structurally related compounds. The luminal transport system can be activated from the luminal side by phosphate.

Animals↗
PubMed1984

Dermatitis herpetiformis: effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity.

The effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity were studied using in vitro assays to measure these parameters. Leukocyte iodination was documented using a quantitative assay to measure the iodination of protein by human neutrophils undergoing phagocytosis. Cytotoxicity for the tumor cell line LSTRA by human neutrophils activated by exposure to phorbol myristate acetate was measured by a 51Cr release assay. Dapsone, diasone, and sulfapyridine, at concentrations comparable to serum levels obtained by therapeutic doses of drug, effectively inhibited iodination and cytotoxicity mediated by human neutrophils. Other sulfonamides showed little inhibition of either iodination or cytotoxicity. The amount of inhibition was comparable to that seen with the inhibitors azide or cyanide and occurred in a dose dependent manner with all three drugs. A cell-free cytotoxic system using myeloperoxidase, iodide, a H2O2 generating system, and target cells also showed inhibition by dapsone, diasone and sulfapyridine in a similar fashion. The active drugs inhibited both the intra- and the extracellular myeloperoxidase-H2O2-halide cytotoxic systems. Serial iodination studies of four dermatitis herpetiformis patients, evaluated while taking dapsone or sulfapyridine, showed inhibition of iodination by either drug. Levels of IgA immune complexes, as measured by the Raji cell radioimmune assay adapted for IgA, did not change when medication was withheld. These studies demonstrate that dapsone, diasone, and sulfapyridine inhibit both neutrophil iodination and cytotoxicity for tumor cells, while other sulfonamides have no effect. This confirms previous studies showing inhibition by myeloperoxidase mediated iodination by dapsone. Furthermore, the effect on neutrophils is quickly reversible; in vivo administered drug has no effect on in vitro function. The active drugs inhibit both intra- and extracellular cytotoxic systems. This may represent an important mechanism by which these drugs produce their therapeutic effects when used to treat inflammatory skin diseases.

Antigen-Antibody Complex↗
PubMed2001

Effect of dichlorophenolindophenol, dichlorophenolindophenol-sulfonate, and cytochrome c on redox capacity and simultaneous net H+/K+ fluxes in aeroponically grown seedling roots of sunflower (Helianthus annuus L.): new evidence for a plasma membrane CN(-)-resistant redox chain.

Excised roots from axenically grown sunflower seedlings reduced or oxidized exogenously added 2,6-dichlorophenolindophenol (DCIP), DCIP-sulfonate (DCIP-S), and cytochrome c, and affected simultaneous H+/K+ net fluxes. Experiments were performed with nonpretreated "living" and CN(-)-pretreated "poisoned" roots (control and CN(-)-roots). CN(-)-roots showed no H+/K+ net flux activity but still affected the redox state of the compounds tested. The hydrophobic electron acceptor DCIP decreased the rate of H+ efflux in control roots with extension of the maximum rate and optimal pH ranges, then the total net H+ efflux ([symbol: see text]H+) equalled that of the roots without DCIP. The simultaneously measured K+ influx rate was first inhibited, then inverted into efflux, and finally influx recovered to low rates. This effect could not be due to uptake of the negatively charged DCIP, but due to the lower H+ efflux and the transmembrane electron efflux caused by DCIP, which would depolarize the membrane and open outward K+ channels. The different H+ efflux kinetics characteristics, together with the small but significant DCIP reduction by CN(-)-roots were taken as evidence that an alternative CN(-)-resistant redox chain in the plasma membrane was involved in DCIP reduction. The hydrophilic electron acceptor DCIP-S enhanced both H+ and K+ flux rates by control roots. DCIP-S was not reduced, but slightly oxidized by control roots, after a lag, while CN(-)-roots did not significantly oxidize or reduce DCIP-S. Perhaps the hydrophobic DCIP could have access to and drain electrons from an intermediate carrier deep inside the membrane, to which the hydrophilic DCIP-S could not penetrate. Also cytochrome c enhanced [symbol: see text]H+ and [symbol: see text]K+, consistent with the involvement of the CN(-)-resistant redox chain. Control roots did not reduce but oxidize cytochrome c after a 15 min lag, and CN(-)-roots doubled the rate of cytochrome c oxidation without any lag. NADH in the medium spontaneously reduced cytochrome c, but control or CN(-)-roots oxidized cytochrome c, despite of the presence of NADH. In this case CN(-)-roots were less efficient, while control roots doubled the rate of cytochrome c oxidation by CN(-)-roots, after a 10 min lag in which cytochrome c was reduced at the same rate as the medium plus NADH did. CN(-)-roots seemed to have a fully activated CN(-)-resistant branch. The described effects on K+ flux were consistent with the current hypothesis that redox compounds changed the electric membrane potential (de- or hyperpolarization), which induces the opening of voltage-gated in- or outward K+ channels.

2,6-Dichloroindophenol↗
PubMed1987

Growth inhibitory effects of dimethyl sulfoxide and dimethyl sulfone on vascular smooth muscle and endothelial cells in vitro.

The growth of bovine aortic smooth muscle and endothelial cells was studied after exposure to dimethyl sulfoxide (DMSO) or its major metabolite, dimethyl sulfone (DMSO2). Both compounds caused a dose-dependent inhibition of cell growth as determined by [3H]thymidine incorporation and by counting the number of cells with time of exposure in culture. The IC50 of DMSO (concentration which produces 50% inhibition of growth) was 1% for smooth muscle cells and 2.9% for endothelial cells. Similarly, the IC50 of DMSO2 was also 1% for smooth muscle cells, but was 1.8% for endothelial cells. After a 4-d exposure to either compound, the growth inhibition of smooth muscle cells was completely reversible at 1%, partially reversible at 2 to 3% and completely irreversible at 4%. By comparison, inhibition of endothelial cell growth was completely reversible up to 4% of either compound. It is concluded that the growth of smooth muscle cells was similarly inhibited by DMSO and DMSO2, but that smooth muscle cells were more susceptible than endothelial cells to the growth inhibitory effects of these compounds. In addition, DMSO2 was a more potent inhibitor of cell growth than DMSO and its growth inhibition was less reversible than that produced by DMSO.

Animals↗
PubMed2004

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors.

Previous studies have shown that proteasome inhibitors are novel agents for chemotherapy of human African trypanosomiasis or sleeping sickness. In this study, five peptide trileucine methyl vinyl sulfones with different N-terminal substituents were tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. Two inhibitors displayed promising anti-trypanosomal activities with ED50 values in the sub-micromolar range. Higher trypanocidal activity of the compounds generally corresponded to a higher k(obs)/[I] value for inhibition of the trypsin-like activity but not for the inhibition of the chymotrypsin-like activity of the proteasome. These data suggest that inhibitors with strong activity against the trypsin-like activity of the proteasome are the rational choice for future anti-sleeping sickness drug development.

Animals↗
PubMed2005

Determination of biodegradation products from sulfonated dyes by Pleurotus ostreatususing capillary electrophoresis coupled with mass spectrometry.

Microbial treatment of environmental pollutants including dyes with white rot fungi has received wide attention as a potential alternative for conventional methods in wastewater treatment. The degradation products from dyes and mechanism underlying fungal degradation of dyes is desirable to be understood. Capillary electrophoresis coupled with mass spectrometry (CE-MS) was used in this study to determine biodegradation products of 4-[(4-hydroxyphenyl)azo]-benzenesulfonic acid, sodium salt (4HABA) and Acid Orange 7 (C.I. 15510), produced by a white rot fungus, Pleurotus ostreatus. Two major degradation products, benzenesulfonic acid and 4-hydroxy-benzenesulfonic acid, from both sulfonated compounds, were identified and their kinetic profiles in biodegradation were followed by CE-MS. Another product, 1,2-naphthoquinone, from Acid Orange 7 was identified using HPLC. Formation of these products in fungal degradation is discussed.

Biodegradation, Environmental↗
PubMed1984

Colorimetric assay for monoamine oxidase in tissues using peroxidase and 2,2'-azinodi(3-ethylbenzthiazoline-6-sulfonic acid) as chromogen.

Monoamine oxidase is assayed in tissue by a colorimetric reaction using horse radish peroxidase and 2,2'-azinodi(ethylbenzthiazoline-6-sulfonic acid to measure H2O2 formed during oxidation of amines. The method has a coefficient of variation of approximately 2.5% and provides results comparable with those of radiometric assay. Monoamine oxidase activities in rat liver mitochondria and crude mitochondrial fraction from brain and with tyramine as a substrate were 18.9 +/- 0.4 and 4.61 +/- 0.15 nmol/min/mg of protein, respectively, using this method. Kinetic parameters of liver and brain monoamine oxidase with various substrates and inhibitors appeared to be the same when determined by either colorimetric or radiometric methods.

Animals↗
PubMed1990

An enzymatic colorimetric method for measuring naringin using 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS) in the presence of peroxidase.

A sensitive colorimetric method for naringin estimation using 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) as peroxidase substrate is described. The method is based on the coupling reaction of an ABTS radical cation with an oxidation product of naringin formed by peroxidase. This coupling reaction leads to the formation of a purple-colored compound with a maximum absorption at 560 nm. A molar absorption coefficient at this wavelength was calculated to be 13,286 +/- 200 M-1 cm-1. The lowest amount of naringin that can be detected is 1 nmol. The application of this method to the quantification of naringin in grapefruit tissues is presented.

Benzothiazoles↗
PubMed1979

Specific sulfonation of tyrosine, tryptophan and hydroxy-amino acids in peptides.

1. ClSO3H in trifluoroacetic acid rapidly converts serine and threonine into O-sulfate ester derivatives while tyrosine and tryptophan are converted into arylsulfonic acids. 2. H2SO4 in trifluoroacetic acid reacts more slowly with serine, threonine and tyrosine while is not able to modify tryptophan. 3. All other amino acids are perfectly stable under the above reaction conditions. 4. Peptides containing susceptible amino acid residues are specifically converted into the corresponding sulfonated derivatives in high or quantitative yield.

Amino Acids↗
PubMed1993

Regulation of cytochrome P450 2B1/2 genes by diallyl sulfone, disulfiram, and other organosulfur compounds in primary cultures of rat hepatocytes.

Our previous study demonstrated that diallyl sulfide (DAS), a compound derived from garlic, transcriptionally activated the P450 2B1/2 genes in rat liver. In the present study, rat primary hepatocytes were used to determine the effects of DAS and its metabolite, diallyl sulfone (DASO2), on the expression of the P450 2B1/2 genes. Freshly isolated adult rat hepatocytes were cultured in a serum-free medium on a reconstituted basement membrane matrix "matrigel" that enabled the hepatocytes to maintain expression of numerous liver-specific genes for more than 1 week. After 48-hr of acclimation, 0.1, 0.5, and 2.0 mM concentrations of DAS or DASO2 were added to the culture medium and the cells were harvested at 4, 12, 24, or 36 hr after the treatment for the preparation of microsomes and RNA. Cytotoxicity was not observed by morphological examinations after DAS and DASO2 treatments. In contrast to the in vivo results, there was only a slight increase in the levels of P450 2B1/2 mRNA and protein in DAS-treated cells. However, DASO2 treatment (2 mM) resulted in 11-, 21-, and 22-fold increases in P450 2B1/2 mRNA levels at 12, 24, and 36 hr after the treatment, respectively. P450 2B1/2 protein levels were also increased markedly in DASO2-treated cells. Co-incubation of the rat hepatocyte cultures with a physiological concentration of growth hormone significantly blocked the induction of P450 2B1/2 mRNA by DASO2. Northern blot analysis using oligonucleotide probes specific for 2B1 and 2B2 demonstrated that DASO2 induced mRNA levels of both 2B1 and 2B2, with a greater induction of 2B1 mRNA. For comparison, the effects of disulfiram (DSF) and its metabolite, diethyldithiocarbamate (DDTC), on P450 2B1/2 mRNA expression were also examined in the cultured rat hepatocytes. Both DSF and DDTC caused a significant increase in P450 2B1/2 mRNA level with the highest induction at 0.5 mM. Addition of growth hormone to the culture effectively suppressed the P450 2B1/2 mRNA induction by DSF but had little effect on the induction by DDTC. Neither mRNA nor protein levels of P450 2E1 in cultured hepatocytes were affected by all the organosulfur compounds tested. These results suggest that DASO2, DSF and DDTC selectively modulate P450 isozymes in cultured rat primary hepatocytes and that the induction of P450 2B1/2 by DAS in rat liver may be mediated by its metabolite, DASO2.

Allyl Compounds↗
PubMed1994

New sulfonated distamycin A derivatives with bFGF complexing activity.

Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been synthesized with the objective of identifying novel compounds able to complex basic fibroblastic growth factor (bFGF) and other factors involved in tumour angiogenesis, and consequently to block the angiogenic process. These new compounds have been characterized for their ability to inhibit bFGF binding, in vivo bFGF-induced angiogenesis and neovascularization of the chorioallantoic membrane, in comparison with suramin. The two most active compounds, FCE 26644 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole)carbonylimino))-bis(1,3-naphthalenedisulfonic acid)] and FCE 27164 [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole) carbonylimino)-bis (1,3,5-naphthalenetrisulfonic acid)] have been selected for extended evaluation. Both compounds are active in inhibiting platelet-derived growth factor beta (PDGF beta) and interleukin-1 beta binding. Two different assays have been performed to study their mode of action: the sequential binding assay on bFGF and PDGF receptors and the bFGF-induced tyrosine phosphorylation assay. The results of the two assays are in agreement and indicate that no activity is observed if FCE 26644, FCE 27164 and suramin are administered as pretreatment, when a direct interaction of the compounds with bFGF and PDGF receptors is required. Conversely, inhibitory activity is observed when the compounds are allowed to form complexes with the growth factors themselves.

3T3 Cells↗
PubMed1977

Determination of free and esterified cholesterol by a kinetic method. I. The introduction of the enzymatic method with 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS).

A new, simple kinetic method is described for the determination of serum cholesterol based on the oxidation of 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS) by use of a single aqueous reagent. This assay procedure is rapid, specific, reproducible and applicable to the measurement of free and esterified cholesterol in a continuous procedure. The method requires no prior treatment of sample and linear kinetics are obtained up to 13 mmol/l cholesterol. The use of ABTS permits the direct calculation of cholesterol concentrations from absorbance changes at 410 nm (A = epsilon - c - d).

Benzothiazoles↗
PubMed1980

Determination of free and esterified cholesterol by a kinetic method. II. Evaluation of the enzymic method which uses 2,2-azino-di(3-ethyl-benzthiazoline-6-sulfonate) (ABTS) as chromogen.

A simple kinetic method for the determination of free and esterified serum cholesterol based on the oxidation of 2,2'-azino-di(3-ethyl-benzthiazoline-6-sulfonate) (ABTS) by use of choilesterol esterase, cholesterol oxidase and peroxidase has already been reported. Here the method is statistically examined. The method is very sensitive and precise (C.V. below 5%). The standard curve is linear up to 25.9 mmol/l. Comparison with results by Abell's method gave a linear regression of Yx = 0.2025 + 1.0043X with a correlation coefficient (r) of 0.983. Comparison with the enzymic methods of Roeschlau et al., Trinder, and Allain et al. gave Yx = 0.2037 + 0.9549X (r = 0.975), Yx = 0.4777 +0.8857X (r = 0.958) and Yx = 0.244 + 0.932X (r = 0.970), respectively. The effects of haemoglobin and bilirubin were studied and normal ranges for the method were determined on 150 healthy mature subjects of both sexes between 20 and 45 years of age. They are 3.375 to 6.948 mmol/l for total cholesterol, and 0.7196 to 2.089 mmol/l for free cholesterol.

Adult↗
PubMed1987

Cryoprotection by dimethyl sulfoxide and dimethyl sulfone.

Preservation of cells and tissues at low temperatures requires the presence of effective cryoprotectants with low toxicity to which cells are relatively permeable. Two similar compounds, dimethyl sulfoxide (DMSO) and dimethyl sulfone (DMSO2), exhibit both features for cryoprotectants, yet DMSO is a very effective cryoprotectant while DMSO2 is ineffective. This anomaly was investigated by relating observations on the phase behavior of DMSO and DMSO2 in aqueous solutions to the recovery of human lymphocytes frozen in the presence of these compounds. The lack of cryoprotection in the presence of DMSO2 appears to be due to the precipitation of DMSO2 from the solution at subzero temperatures. The observation of reduced cell recovery after freezing with increasing concentrations of DMSO2 implies that cell damage is related to the amount of solid DMSO2 present. Precipitation of DMSO2 occurs both intra- and extracellularly, but it is argued that intracellular precipitation of DMSO2 is the damaging phenomenon. Cryoprotective compounds are normally selected based on the criteria of low toxicity and permeability to the plasma membrane. An additional condition, solubility, must be included for interpretation of experimental data and for development of effective protocols for cryopreservation.

Cell Survival↗
PubMed1993

Intraperitoneal administration of leukotriene B4 (LTB4) and omega-guanidino caproic acid methane sulfonate (GCA) increased the survival of mice challenged with methicillin-resistant Staphylococcus aureus (MRSA).

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) very often complicate management of immunocompromised patients. We studied the effect of leukotriene B4 (LTB4) and epsilon-guanidino caproic acid methane sulfonate (GCA), on MRSA infection. Mice fed a 20% casein diet were intraperitoneally administered LTB4, GCA, or saline (control) daily for 30 days. On the 10th day of this treatment, mice were challenged with MRSA. The survival rate in the control group (20%) was significantly lower than the rates in the GCA (60%) and LTB4 (50%) groups, respectively (p < 0.05). There was a significant reduction of MRSA in the spleen and kidney of the survived mice in GCA group as against mice in the LTB4 and saline groups, indicating a better recovery in GCA group than the other groups. The results suggest that intraperitoneal administration of GCA and LTB4 may play a role in host defense mechanism during MRSA infections.

Animals↗
PubMed1991

Topical treatment of multiple actinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double-blind, comparative study.

In a double-blind, randomized, within-patient comparative study, the efficacy and tolerability of Ro 14-9706 (an arotinoid methyl sulfone) in the treatment of actinic keratoses was compared with that of tretinoin (all-trans-retinoic acid). A total of 25 patients with more than three lesions on each side of the face completed the study. All patients applied each agent twice daily for 16 weeks as a 0.05% cream to opposite sides of the face. The number of actinic keratoses in each treatment area was counted before treatment and at weekly intervals. The mean percent decrease in the number of actinic keratoses was 37.8% for areas treated with Ro 14-9706 and 30.3% for areas treated with tretinoin. Each of these decreases was significantly different from baseline (p less than 0.01), but not from each other. Ro 14-9706 was better tolerated; local inflammation was slight or absent in most patients, whereas tretinoin caused severe erythema in 50% and severe scaling in 23% of patients.

Administration, Cutaneous↗