Thiol Compounds Glutathione Research Articles

Inhibitory effect of thiol compounds on browning precursors and intermediates in sorbitol/glycine system.

Sorbitol as a sweetener is often thought to be unable to participate in the Maillard reaction causing browning. However, browning of a system was found to be significant when sorbitol was mixed with glycine and heated. The thiol compounds glutathione and cysteine were added to the system, and the inhibition mechanism of the two on the browning of the system was studied by combining the changes of precursor substances, intermediate products and browning degree. When the concentration of thiol compounds reached 25 mg mL-1, both could make the browning inhibition of the system more than 80%, and the accumulated glucose concentration was reduced to <35% of the control. The production of 3-deoxyglucosone, a precursor of melanoidin, was significantly reduced. Glutathione and cysteine directly inhibited the production of substrates in the sorbitol/glycine system, reduced glucose accumulation through competitive consumption and captured highly active intermediates through sulfhydryl groups. This has implications for the browning control of food systems containing sugar alcohols. © 2024 Society of Chemical Industry.

The thiol compounds glutathione and homoglutathione differentially affect cell development in alfalfa (Medicago sativa L.)

Glutathione (GSH) is an important scavenger of Reactive Oxygen Species (ROS), precursor of metal chelating phytochelatins, xenobiotic defence compound and regulator of cell proliferation. Homoglutathione (hGSH) is a GSH homologue that is present in several taxa in the family of Fabaceae. It is thought that hGSH performs many of the stress-defence roles typically ascribed to GSH, yet little is known about the potential involvement of hGSH in controlling cell proliferation. Here we show that hGSH/GSH ratios vary across organs and cells and that these changes in hGSH/GSH ratio occur during dedifferentiation and/or cell cycle activation events. The use of a GSH/hGSH biosynthesis inhibitor resulted in impaired cytokinesis in isolated protoplasts, showing the critical importance of these thiol-compounds for cell division. However, exposure of isolated protoplasts to exogenous GSH accelerated cytokinesis, while exogenous hGSH was found to inhibit the same process. We conclude that GSH and hGSH have distinct functional roles in cell cycle regulation in Medicago sativa L. GSH is associated with meristemic cells, and promotes cell cycle activation and induction of somatic embryogenesis, while hGSH is associated with differentiated cells and embryo proliferation.

The Effect of Thiols and Rhizopon on the Rooting of Woody Stem Cutting of Punica granatum L.

A research study was established to determine the effect of thiol compounds glutathione (GSH) and dithiothreitol (DTT) to induce rooting and root growth of woody stem cuttings from Punica granatum L., either alone or in combination with rhizopon. Woody cuttings of P. granatum 10 cm long were collected from 5-year-old potted greenhouse grown plants. No leaves were left attached on the cuttings. The proximal end of cuttings were dipped for 10 sec in 0.05 and 0.1 mM of GSH; 0.6, 1, and 2 mM of DTT followed by a 5-min rest, and immediately dipped in a solution of 1500 ppm of Rhizopon for 10 sec. Untreated cuttings were used as control as well as cuttings dipped only in 1500 ppm of Rhizopon for 10 sec. Rooting was continuous with bottom heating at 24 °C under greenhouse conditions. The experimental data was analyzed statistically using a completely randomized block design with five replications. The average total number of roots was increased when the cuttings were treated with the thiol compounds and Rhizopon, 52 days after treatment. However, DTT at 1.0 mM increased more significantly the average total number of roots than GSH at any concentration. The presence of DTT alone at 1.0 mM or with 1500 ppm of Rhizopon increased the average number of roots to 10.04 and 10.99, respectively. No significant difference was found for the treatment of 0.05 mM GSH and 1500 ppm Rhizopon showing average number of 12.11 roots. Significant average total root length was detected in cuttings treated with 1500 ppm Rhizopon compared to control, GSH at 0.1 mM, and DTT at 0.6 mM and 1.0 mM.

WR2721 as a modulator of cisplatin- and carboplatin-induced side effects in comparison with other chemoprotective agents: a molecular approach.

Cisplatin is an active cytostatic that became successful in the treatment of several types of solid tumours after its nephrotoxic potential was controlled by hydration and diuresis. Thiol compounds were tested to reduce further cisplatin-induced nephrotoxicity. Thiosulphate is rapidly excreted by the kidneys and protects against cisplatin-induced nephrotoxicity by inactivating reactive platinum species in the kidney. Due to inactivation of cisplatin in the circulation, thiosulphate also interferes with its antitumour activity. Therefore, it is mainly used in two-route schedules, whereby cisplatin is delivered locally to the tumour (i.p. or i.a.) while systemic (i.v.) thiosulphate protects the kidneys. Diethyldithiocarbamate was shown to protect against cisplatin-induced nephrotoxicity in several animal models by reversing cellular damage. However, in the clinic it has been less successful, partly due to its central nervous system toxicity. The endogenous thiol compounds glutathione and metallothionein have been shown to reduce cisplatin-induced toxicity both in animal models and in clinical trials. However, the results are rather preliminary and a reduction in therapeutic efficacy may be expected, for both glutathione and metallothionein have been reported to be involved in platinum resistance. The thioether methionine has been shown to reduce cisplatin-induced nephrotoxicity in animal models but it has not yet been tested in the clinic. Cisplatin-induced acute emesis can be sufficiently controlled with a new class of 5-hydroxytryptamine-3 (5HT3)-receptor blockers, but delayed emesis remains a problem. High-dose cisplatin regimens with protection of the kidneys induces ototoxicity, peripheral neuropathy and myelotoxicity, which become dose-limiting. Neurotoxicity was partly reversed by the neurogenerative agent ORG2766, but this agent does not reduce other cisplatin-induced toxicities. Therefore, an agent capable of protecting multiple non-tumour tissues is needed. Carboplatin is a second-generation analogue of cisplatin with less nephro-, neuro- and ototoxicity. Carboplatin is at least as active as cisplatin at its maximum tolerated dose, which is defined by its myelotoxicity. Protection from carboplatin-induced myelotoxicity may be controlled by autologous bone marrow transplantation and/or hematopoietic growth factor infusions. High-dose carboplatin schedules may cause nephrotoxicity, neurotoxicity and ototoxicity. Again, the protection of multiple non-tumour tissues is needed. WR2721 appears to be such a modulating agent capable of protecting multiple non-tumour tissues. It was shown to be preferentially metabolized and taken up as the thiol metabolite WR1065 by non-tumour tissues as compared with (hypoxic) solid tumours. It was shown to protect mice from cisplatin-induced nephrotoxicity and from cisplatin- and carboplatin-induced myelotoxicity without interfering with the antitumour activity.(ABSTRACT TRUNCATED AT 400 WORDS)

The anti-inflammatory activity of Ebselen but not thiols in experimental alveolitis and bronchiolitis

This paper describes the effects of the thiol compounds glutathione and N-acetylcysteine and the seleno-organic agent Ebselen on the development of Sephadex-induced lung edema and cell infiltration in the rat. Neither thiol had any effect upon the development of the edema when administered in large, repeated doses. In contrast, when Ebselen was co-administered with the thiols, there was a dose-dependent inhibition of the development of the edema, but lung weights could not be returned to normal values. However, when the thiols were omitted and Ebselen was administered alone, the development of the edema was totally blocked. In addition, in Ebselen-only treated animals there was a selective inhibition of the infiltration of lymphocytes, basophils and eosinophils into the lung lumen without affecting the populations of macrophages and neutrophils. Again, the Ebselen-induced effect was reduced by coadministration of either thiol. These findings are discussed in terms of the potential mechanism of action of Ebselen in vivo and of the possibility of Ebselen being of therapeutic potential in cases of diffuse pulmonary inflammation in humans.

Thimerosal induces endothelium-dependent vascular smooth muscle relaxations by interacting with thiol groups. Relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF).

The sulfhydryl reagent thimerosal, as well as acetylcholine and Ca2+-ionophore A23187, produced concentration-dependent relaxations of intact rabbit aortic strips. The ability of strips to relax in response to these agents was dependent on the presence of vascular endothelium. Purposely removing the endothelium led to a complete loss of the relaxation responses. Thimerosal was at least as efficacious as A23187 in inducing endothelium-dependent relaxations, but its relaxations developed much slower than those induced by A23187 or acetylcholine. A small concentration of thimerosal that had no appreciable effect by itself, potentiated the relaxing response to acetylcholine in endothelium-intact preparations. Endothelium-dependent relaxations induced by larger concentrations of thimerosal, as well as relaxations produced by acetylcholine, were inhibited by the antioxidant and lipoxygenase inhibitor nordihydroguaiaretic acid, by haemoglobin, and by the inhibitor of soluble guanylate cyclase methylene blue. Indomethacin had no effect on these relaxations. The thiol compounds glutathione, 2-mercaptoethanol and a low concentration of dithiothreitol prevented (and reversed) relaxations induced by thimerosal, but had little or no effect on ACh relaxations. A high concentration of dithiothreitol also markedly inhibited the ACh relaxation. These results are consistent with the hypothesis that thimerosal stimulates endothelial cells to produce a relaxing substance whose properties are similar or the same as those of the endothelium-derived relaxing factor (EDRF) released in response to acetylcholine or A23187. The biochemical mechanism by which thimerosal induces the formation and/or release of this relaxing substance is likely to be different from ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of cyclophosphamide metabolites with membrane proteins: An in vitro study with rabbit liver microsomes and human red blood cells : Effect of thiols

Cyclophosphamide metabolites have been generated in vitro by microsomal oxidation of cyclophosphamide and their binding to rabbit liver microsomes and to intact human red blood cells has been investigated. Reactions with proteins of membrane and cytoplasm were detected by SDS polyacrylamide gel electrophoresis. The protein bands were analysed for incorporation of radioactivity. The following results were obtained. (1) Preferential binding of acrolein to microsomes and erythrocytes, with only little binding of metabolites containing the chloroethyl moiety. (2) Reduction of acrolein binding by the thiol compounds glutathione, 2,3-dimercaptopropane-1-sulfonate and mercaptoethane sulfonate. (3) In microsomes: formation of protein polymerisation products and incorporation of radioactivity. (4) In red blood cells: cross-linking of membrane proteins and formation of globin dimerization products in the cytoplasm.