Property of a new Prussian blue-bounded iron complex able to peroxidate non-saturated fatty acids with a tendency to create conditions that may encourage ferroptosis.

Ferroptosis is a cell death process caused by redox imbalance in the cell environment. However, the cell death pathway proves beneficial in anticancer therapy, so compounds inducing ferroptosis are sought. The paper presents a newly synthesized iron complex named FeT, composed of ferricyanide and tartrate, which seems to meet these expectations. It is relatively stable, easily soluble in water and capable of peroxidating unsaturated fatty acids. T24 bladder cells were used as model cells. Preliminary studies demonstrated a strong inhibitory effect of this compound on cell proliferation. The cytotoxicity of FeT was assessed. Independently, it initiates caspase activity, indicating the complex cellular impact of this compound. This effect is compellingly the result of FeT penetration into the cell's interior with possible direct damage to mitochondria, thus explaining the involvement of apoptosis in cell death. At the same time, after penetrating into the cell, it causes an increase in reactive oxygen species (ROS), lipid peroxidation and a decrease in reduced glutathione, which is interpreted as to cause ferroptosis. In turn, reducing mitochondrial potential may indicate both ferroptosis and an internal pathway to apoptosis.

Effects of diallyl disulfide and other donors of sulfane sulfur on the proliferation of human hepatoma cell line (HepG2).

Effects of potential sulfane sulfur precursors (diallyl disulfide, cystamine, 2-mercaptoethanol disulfide, thiosulfate, immunothiole and pyridoxal phosphate jointly with cystine) on [3H]-thymidine incorporation in human hepatoma (HepG2) cells were studied. Of the tested compounds, diallyl disulfide, cystamine and 2-mercaptoethanol disulfide were found to cause significant inhibition of HepG2 cells proliferation. Moreover, pyridoxal phosphate jointly with cystine suppressed [3H]-thymidine incorporation, but the differences between that system and control cells were insignificant. In the case of thiosulfate, no significant difference was observed. The present study shows that diallyl disulfide, found in garlic, is effective in inhibiting [3H]-thymidine incorporation in human hepatoma HepG2 cell cultures. Similar antiproliferative effects on HepG2 cells are shown by such systems being a source of sulfane sulfur as cystamine or 2-mercaptoethanol disulfide. Thus, it may be concluded that these donors of reactive sulfane sulfur may be responsible for inhibition of the proliferation of HepG2 cells. It is suggested that the observed antiproliferative properties of the investigated compounds are connected with the presence of the highly reactive sulfane sulfur.

Various forms of plasma cysteine and its metabolites in patients undergoing hemodialysis.

The thiol tripeptide glutathione (GSH) is particularly important as an antioxidative protector in the cells. GSH is also a form of storage and transport of cysteine. Under physiological conditions, the kidney plays an essential role in GSH biodegradation to free cysteine via gamma-glutamyl cycle and subsequently in further metabolism of this sulfur amino acid. Our aim was to assess to what degree renal insufficiency affects the level of various cysteine forms and its metabolites (sulfates and sulfane sulfur compounds) in the plasma, and whole blood GSH levels. The concentrations of all the above mentioned sulfur compounds were measured in plasma of patients with end stage renal failure (ESRF) before and after dialysis and in a group of healthy controls. In plasma of patients with ESRF before dialysis tendency towards significant elevation of cystine, protein-bound cysteine and sulfates levels was evident. Simultaneously, a decrease of plasma level of sulfane sulfur compounds, products of anaerobic sulfur metabolism, and whole blood GSH concentration was found. As a consequence, the ratio between the reduced cysteine and the total cysteine concentration was markedly decreased. The dialysis session restore this ratio to the value observed in plasma of control individuals. These findings indicate disturbances in the thiol-disulfide equilibrium and show a higher oxidation status in plasma of patients with ESRF than in healthy controls.

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.

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.