| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Diallyl trisulfide (DAIS) and diallyl disulfide (DADS), oil-soluble components of garlic, were shown to induce phase II enzymes in vitro and in vivo. The detailed mechanism of induction activity of these compounds has not been elucidated completely, although several hypotheses have been proposed. To establish the role of redox stress involved in induction of phase II enzymes by the Album polysulfides, we compared the ability of mono-, di- and trisulfides to generate ROS, the ESR spectrometry and the GST (glutathione S transferase) induction activity in rat liver epithelial RL34 cells. The proposed mechanisms of redox stress between the Album polysulfides and glutathione (GSH) were also discussed.
The polysulfides were tested for the inducing ability of ROS levels by means of DCF fluorescence in RL34 cells. Trisulfides were successfully demonstrated to generate free radicals in RL34 cells in order of DATS (diallyltrisulfide) > DADS (diallyldisulfide) > DAS (diallylsulfide). In the ESR experiment, the hydroxyl radicals were gradually detected from half hour after the reaction initiated by adding trisulfides with GSH. These data suggested that the redox cycling between trisulfides and GSH was likely to go along according to the polysulfide-thiol pathway, which products were reported to be superoxide and unstable perthiol (RSSH).
On the other hand, the induction activity of QR (quinone reductase) was also measured in RL34 cells. Not only trisulfides but also disulfides potently induced QR, especially DADS. DADS with thiols could not be detected any signals in the ESR experiment. We considered that DADS might preferentially be metabolized to a certain strong electrophile. We supposed that allicin (diallylthiosulfinate), a strong electrophile, was generated from DADS by metabolism of CYP2E1 as one possible candidate. However, the inductions of any CYPs were not detected in addition of DADS in RL34 cells.
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