Project/Area Number |
06660165
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
食品科学・栄養科学
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Research Institution | Nihon University |
Principal Investigator |
ARIGA Toyohiko Nihon Univ., Agric.Vet.Med., Professor, 農獣医学部, 教授 (50096757)
|
Co-Investigator(Kenkyū-buntansha) |
ISHII Kenji Nihon Univ., Agric.Vet.Med., Professor, 農獣医学部, 教授 (80058776)
SAKURAI Hidetoshi Nihon Univ., Agric.Vet.Med., Assoc.Prof., 農獣医学部, 助教授 (80059617)
KUMAGAI Hitomi Nihon Univ., Agric.Vet.Med., Lecturer, 農獣医学部, 専任講師 (20225220)
SEKI Taiichiro Nihon Univ., Agric.Vet.Med., Lecturer, 農獣医学部, 専任講師 (20187834)
|
Project Period (FY) |
1994 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | Garlic / Platelet / Arachidonic acid / Prostaglandin / Thromboxane / Cyclooxygenase / Aspirin / Endothelial cells / 血小板擬集 / メチルアリルトリスルフィド / 血小板 / トロンボキサンシンセターゼ |
Research Abstract |
A potent platelet aggregation inhibitor, methyl allyl trisulfide (MATS) found in the steam distillled oil components from garlic (Allium sativum L.) was studied to reveal its inhibition mechanism. MATS suppressed synthesis of thromboxane A_2 (TXA_2) in platelets, and showed quite different mode of inhibition from the most of all known specific inhibitors, e.g., aspirin for cyclooxygenase (COX) , esculetin for lipoxygenase (LPX) and OKY-046 for thrombaxane synthase (TXS). MATS inhibited both COX and LPX,but TXS at the concentration lower 10^<-4>M.MATS was judged to inactivate prostaglandin endoperoxide synthase (PGH synthase) , however, the inhibition was confined to the direction toward one of its activities, peroxidase activity. COX activity the another activity of this bifunctional enzyme, which has been found to be inhibited specifically by aspirin, seemed to be unaffected by MATS,since arachidonic acid was consumed with the metabolic rate similar to the control. Although, the detailed interaction between MATS and PGH synthase is not demonstrated yet, MATS would prevent the reduction of a substrate (PGG_2) through its alkyl sulfides structure. Against PGI_2 generation by the endothelial cells of aortic vessel walls, MATS also affected to reduce its levels. These results made us suspicious whether MATS acts practically antithrombotic. Then, we are about to investigate in vivo effect of MATS using an animal model of thrombosis.
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