| The health benefits of Allium vegetables are widely attributed to the enzyme produced organosulfur compounds called thiosulfinates (TS) and related compounds. This dissertation research is focused on the cysteine and glutathione mixed disulfide conjugates of TS (CySSR/GSSR, R = methyl, ethyl, propyl, 1-propenyl and allyl). These conjugates are the presumptive in vivo metabolic products of TS.;Gram-scale CySSR/GSSR were prepared by the reaction of dithiophosphoric-alk(en)yl disulfide with cysteine or glutathione in aqueous solution. The prepared conjugates induced quinone reductase (QR) in Hepa 1c1c7 cells and inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells, indicating they may have potential cancer preventive and anti-inflammatory activities.;A chemoenzymatic method using Allium tissue homogenates was developed to prepare gram-scale TS, including those enriched in 1-propenyl groups which are particularly difficult to obtain. The prepared TS were further utilized to prepare CySSR/GSSR. A genral order of potency of CySSR/GSSR observed was: 1-propenyl > allyl > propyl ≈ ethyl ≈ methyl in terms of QR induction and NO inhibition assays, except that CySSPe showed a weaker NO inhibitory activity than CySSA.;The disulfide bond was found to be critical for the effects of CySSR species. Multiple cellular effects of CySSR were dose-dependently reversed by exogenously added glutathione and N-acetyl cysteine, but not by ascorbic acid. The implicated redox-related mechanism of action of CySSR was related to a glutaredoxin-dependent metabolism of CySSR to generate cysteine and RSH, some of which were subsequently secreted into extracellular medium. A previously proposed beta-lyase-dependent mechanism of CySSR action was indicated to not be involved in the effects of CySSR.;Organoselenium compounds, including benzeneselenol, dibenzyl diselenide, diphenyl diselenide and ebselen, but not the inorganic selenium compound sodium selenite, modulated extracellular redox status via two different mechanisms in macrophage RAW 264.7 cells: (1) induction of cystine- and glucose-dependent extracellular cysteine production through a process via cystine/glutamate antiporter, and (2) induction of cell surface thioredoxin reductase expression, leading to enhanced extracellular reducing capacity. The extracellular redox modulating effects of selenium compounds could be correlated with action mechanism of selenium compounds. |
