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Biomedical subjects

L Włodek

Publications and source records attributed to L Włodek.

16 recordsLinked to original sources
PubMed2001

[Why does nitroglycerin tolerance appear?].

Nitroglycerin (NTG) and other organic nitrates are beneficial drugs for the treatment of acute forms of coronary artery disease. The major limitation of organic nitrates use in clinical practice is the rapid development of hemodynamic tolerance. In general mechanisms of tolerance can be categorized into two different groups. One group of mechanisms is related to changes in the vascular smooth muscle bioactivation of organic nitrates. The other mechanisms are related to physiological response to increase nitric oxide (NO) production.

Acute Disease↗
PubMed1999

The effect of nitrogen oxide level modulation on the content of thiol compounds and anaerobic sulfur metabolism in mice brains.

Aminoguanidine (AG) an inhibitor of NO-synthase reduces cysteine (Cys), cystine (CC), sulfane sulfur (SS) and glutathione (GSH) in brain stems but practically has no effects on the levels of reactive oxygen species (ROS). In cortex AG decreases to a lower degree the concentration of Cys, CC, GSH but in this brain part significantly decreases ROS levels and increases SS. Under the AG action cystathionase (CST) activity very seriously decreases in stems and in cortex and simultaneously activity of 3-mercaptopyruvate sulfurtransferase (MPST) increases. The morpholinosydnonimine (SIN-1) the specific donor of NO and O2 only slightly reduces Cys and GSH in brain stems and ROS and SS remain at the control levels. Simultaneously, there is an increase in cortex of the amounts of GSH with the reduction of ROS and SS. Furthermore, SIN-1 seriously decreases in stems and cortex the activity of CST and increases the activity of MPST. These results confirmed the relationship between intracellular levels of NO, sulfhydryl groups, ROS, and anaerobic sulfur metabolism.

Anaerobiosis↗
PubMed1997

2-Methyl-thiazolidine-2,4-dicarboxylic acid protects against paracetamol induced toxicity in human liver derived HepG2 cells.

The effects of 2-methyl-thiazolidine-2,4-dicarboxylic acid (CP) on paracetamol-induced toxicity were investigated and evaluated in a human liver derived HepG2 cell line. Incubation of the cells with CP (2 mM and 10 mM) drastically attenuated the GSH and cysteine depletion caused by toxic concentrations of paracetamol (1 mM and 5 mM). When CP (10 mM) was introduced alone into the medium, the level of malondialdehyde and the reactive oxygen species were maintained at the control levels with a simultaneous increase of non-protein sulfhydryl in the cells. Thus, the results of our work prove that CP is a non-toxic precursor of cysteine and GSH, and successfully prevents paracetamol toxicity in HepG2 cells.

Acetaminophen↗
PubMed1996

Selective effect of 2-(polyhydroxyalkyl)-thiazolidine-4-carboxylic acids on nonprotein sulfhydryl groups in tumor bearing mice.

1. Thiazolidine derivatives (TD), the products of condensation of L-cysteine (cys) with sugars (D-glucose, D-xylose, D-arabinose, D-galactose, and D-mannose), successfully elevated nonprotein sulfhydryl (NPSH) levels in livers of Ehrlich ascites tumor (EAT)-bearing mice. 2. At the same time, TD promoted a significant drop of NPSH in EAT cells. 3. Thus, TD, through their selective influence on the levels of NPSH in liver and cancer cells appear to be promising compounds for anticancer therapy.

Animals↗
PubMed1996

Sulfurtransferases activity and the level of low-molecular-weight thiols and sulfane sulfur compounds in cortex and brain stem of mouse.

The level of 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese activity and the level of sulfane sulfur compounds, L-cysteine and non-protein sulfhydryl groups (NPSH) were compared in cortex and brain stem of mouse. The level of cysteine and sulfane sulfur compounds was higher in brain stem; 107% and 217% of the value determined in cortex, respectively. The activity of MPST and rhodanese showed also increased level in brain stem; 114% and 119% of the value determined in cortex, respectively. The level of NPSH in cortex was about 10% higher in comparison to brain stem. It seems that in brain stem metabolism of sulfane sulfur compounds and/or their accumulation may occur in a higher degree than in cortex.

Animals↗
PubMed1995

The modulation of IL-2 dependent proliferation of CTLL-2 cells by 2-methyl-thiazolidine-2,4-dicarboxylic acid.

It is known that cysteine and other thiol compounds are able to modulate the immune response. The extracellular concentration of cysteine was shown to determine the intracellular level of glutathione (GSH). Thus cysteine, by enhancing GSH production, is able to affect some T-cell functions like IL-2 dependent cell proliferation and the generation of cytotoxic T cells. However, physiologically blood plasma cysteine is maintained at a very low concentration. The use of cysteine as a therapeutic compound in vivo is strongly limited due to its cytotoxicity. Recent studies demonstrate that N-acetyl-cysteine (NAC) as well as a variety of thiazolidine derivatives (TDs), which are the products of the reaction of L-cysteine with carbonyl compounds, could serve as a 'delivery' system for cysteine into the cell. In the present study, we have shown that 2-methyl-thiazolidine-2,4,-dicarboxylic acid (CP), the product of condensation of L-cysteine and pyruvate, strongly increases the proliferation of one particular cell line, IL-2 dependent CTLL-2 cells. We have also shown that this compound significantly increases the intracellular level of non-protein sulfhydryls (NPSH), but we did not find any correlation between NPSH levels and cell viability and proliferation. In contrast to CP, free cysteine showed its toxic properties by affecting cell viability of different cell lines and also by cancelling the influence of CP on the proliferation of CTLL cells.

Adjuvants, Immunologic↗
PubMed1993

The effect of 2-substituted thiazolidine-4(R)-carboxylic acids on non-protein sulphydryl levels and sulphurtransferase activities in mouse liver and brain.

2-Substituted thiazolidine-4(R)-carboxylic acids (TD) were found to increase the concentration of non-protein sulphydryls (NPSH) and the activity of rhodanese (thiosulphate sulphurtransferase, EC 2.8.1.1) and 3-mercaptopyruvate sulphurtransferase (EC 2.8.1.2) in mouse liver. These properties suggest TDs are potentially hepatoprotective compounds. However TDs also cause depletion of NPSH in the mouse brain and this may be the reason for their toxic side effects on the central nervous system.

Animals↗
PubMed1993

Transamination and transsulphuration of L-cysteine in Ehrlich ascites tumor cells and mouse liver. The nonenzymatic reaction of L-cysteine with pyruvate.

1. The activity of cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese is much lower in Ehrlich ascites tumor cells (EATC) than in mouse liver. 2. Contrary to mouse liver homogenate, no synthesis of sulphane sulphur-containing compounds from L-cysteine is observed in EATC homogenate. 3. 2-Methyl-thiazolidine-2,4-dicarboxylic acid (CP), 2-methyl-thiazolidine-4-carboxylic acid (CA) and thiazolidine-4-carboxylic acid (CF) can be used as sources of low molecular-weight thiol compounds both in EATC and mouse liver homogenate. 4. Pyruvate formed from phosphoenolpyruvate (PEP) in EATC homogenates reacts with L-cysteine (L-CYS) to CP.

Amines↗
PubMed1988

The reaction of sulfhydryl groups with carbonyl compounds.

The sulfhydryl groups of L-cysteine and reduced glutathione (GSH) react nonenzymatically with formaldehyde (F), acrolein (Al), acetaldehyde (AA), malondialdehyde (DAM), pyruvate (P), oxoglutarate (oxo-G) and glucose (G) to form thiazolidine derivatives. These reactions show different velocities and the adducts formed show different stabilities. The equilibrium constants K, as well as the rate constants kr for the reverse reaction, show considerable variation. The carbonyls reveal higher reactivity with sulfhydryl group of L-Cys than with those of GSH, and the stability of the adducts is higher than that of GSH. Al, F and AA react more rapidly with both thiol compounds than the other carbonyls, but the adducts are less stable. The sulfhydryl groups level of bovine serum albumin as well as those of high- and low-molecular thiols of human plasma is reduced in the presence of Al, F or DAM.

Chemical Phenomena↗
PubMed1984

Formation of 2-methyl-2,4-thiazolidinedicarboxylic acid from L-cysteine in rat tissues.

The adduct formed non-enzymatically from L-cysteine and pyruvate: 2-methyl-2,4-thiazolidinecarboxylic acid (CP) was isolated, and identified by the electron impact mass spectroscopy. It was found that CP is formed (by cysteine transformation) and is metabolized in rat tissues. Formation of CP from cysteine or cystine was catalysed by partially purified rat liver gamma-cystathionase.

Animals↗
PubMed1982

3-Mercaptopyruvate sulphurtransferase from rat erythrocytes.

3-Mercaptopyruvate sulphurtransferase (EC 2.8.1.2) was isolated from rat erythrocytes and purified to apparent homogeneity. On disc electrophoresis and isoelectric focusing the enzyme showed microheterogeneity; four enzymatically active microzones of isoelectric points ranging from 5.5 to 7.5, resistant to neuraminidase treatment were detected. The molecular mass of the enzyme determined by the density gradient ultracentrifugation, gel filtration and sodium dodecyl sulphate polyacrylamide-gel electrophoresis was found to be about 36,000. The enzyme is a sialoprotein composed of 219 amino acid and 38 carbohydrate residues. Kinetic parameters of 3-mercaptopyruvate sulphurtransferase from rat erythrocytes were similar to those found for the enzymes isolated from rat liver and Escherichia coli. The purified enzyme was very unstable; spontaneous inactivation could be partly prevented by glycerol (1:5, v/v).

Amino Acids↗
PubMedDate not supplied

Protective effect of alpha-keto acids on the oxidative hemolysis.

We studied antioxidative properties of various concentrations (0.3-2 mM) of biochemically important alpha-keto acids: pyruvate, alpha-ketoglutarate, oxaloacetate, glyoxylic acid as aldehyde acid and also 2-methyl-thiazolidyne-2,4-dicarboxylic acid and their effect on the oxidative hemolysis of human erythrocytes induced by hydrogen peroxide (H2O2). Normal erythrocytes proved to be very resistant to oxidative damages, so the high concentration of H2O2 (10 mM) as well as the presence of natrium azide, a catalase inhibitor, was necessary. The levels of malonyldialdehyde (MDA), reactive oxygen species (ROS) and hemoglobin (Hb) released were evaluated as the measure of red cell peroxidative hemolysis. Pyruvate, at the lowest used concentration (0.3 mM), caused the inhibition of lipid peroxidation (MDA) and a drop in the level of ROS, as well as a diminution of the degree of hemolysis and the effects were stronger than those of other alpha-keto acids. At the highest (2 mM) concentration, the protective effect against oxidative damage of all the investigated alpha-keto acids was similar and amounted to nearly 50% in relation to the control sample. On the contrary, in the case of aldehyde acid, e.g. glyoxylic acid, no protective effect in the same range of concentrations was found. This confirms the participation of non-enzymatic oxidative decarboxylation of alpha-keto acids in the hydrogen peroxide decomposition process.

Adult↗
PubMedDate not supplied

Effect of thiol drugs on the oxidative hemolysis in human erythrocytes.

The effect of different thiol drugs and 2-methyl-thiazolidine-2,4-dicarboxylic acid on the oxidative stress, induced by hydrogen peroxide, was examined in human erythrocytes. The results indicated that captopril (CA), methimazole, N-acetylcysteine (NAC), penicillamine and precursor of L-cysteine 2-methyl-thiazolidine-2,4-dicarboxylic acid (CP) might protect the erythrocyte membrane against lipid peroxidation in the experimental conditions. Captopril, methimazole and penicillamine had the strongest antioxidative properties at the concentration level of 0.5 mM. The protective effects gradually decreased at higher and lower concentrations of these drugs. Contrary, the antioxidative properties of N-acetylcysteine increased with its levels growing in the reaction mixture, and only N-acetylpenicillamine did not protect erythrocytes against oxidative damages. The effect of 2-methyl-thiazolidine-2,4-dicarboxylic acid showed in these in vitro experimental conditions that it could act as an antioxidant at the concentration as high as 5 mM and higher.

Acetylcysteine↗
PubMedDate not supplied

Biosynthesis and biological properties of compounds containing highly reactive, reduced sulfane sulfur.

The covalent modifications of sulfhydryl groups (-SH) may occur through oxidation to mixed disulfides (S-thiolation), S-nitrosylation, as well as persulfide and trisulfide formation. The latter possibilities of -SH group modification connected with compounds containing sulfur called sulfane sulfur are described in this paper. Sulfane sulfur compounds contain a labile, highly reactive sulfur atom at a reduced oxidation state with a valence of 0 or -1, covalently bound to another sulfur atom. These compounds include persulfides, polysulfides, polythionates, thiosulfate, elemental sulfur and disulfides, which enable tautomerization to thiosulfoxides. Sulfane sulfur compounds are formed in the anaerobic cysteine sulfur metabolism with the participation of such enzymes as cystathionase (CST), 3-mercaptopyruvate sulfurtransferase (MpST) and rhodanese (thiosulfate: cyanide sulfurtransferase). Compounds containing sulfane sulfur participate in cell regulation processes through activation or inactivation of some enzymes. Other important roles of sulfane sulfur compounds are their antioxidative properties, significance in the processes of carcinogenesis, participation in the tRNA sulfuration as well as an influence on the activity of immune cells. To recognize completely the biological role of compounds with sulfane sulfur it is necessary to have sensitive methods of quantitative determination, so a review of these methods is presented in this paper. Moreover, biosynthetic pathways and biological properties of these compounds have been discussed.

Animals↗
PubMedDate not supplied

The antioxidative properties of thiazolidine derivatives.

Antioxidative properties of thiazolidine compounds, adducts of L-cysteine with formaldehyde (thiazolidine-4-carboxylic acid), with pyruvate (2-methyl-thiazolidine-2,4-dicarboxylic acid), and glucose (2-/D-gluco-1',2',3',4',5'-penthahydroxypentyl/- thiazolidine-4-carboxylic acid) were studied. The investigated compounds, as well as L-cysteine and DL-penicillamine inhibited in vitro lipid peroxidation induced by NADPH, ethanol, and hydrogen peroxide in the suspension of rat liver microsomes.

Animals↗