1996 Fiscal Year Final Research Report Summary
Development of method for quantitative analysis of neurotoxin candidates ; isoquinolines and heterocyclic amines in food.
| Project/Area Number |
07660145
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | KONAN WOMEN'S JUNIOR COLLEGE |
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Principal Investigator |
TAKAHASHI Tsutomu KONAN WOMEN'S JUNIOR COLLEGE,Food and Nutrition, Professor, 生活科学科, 教授 (20099485)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Cytotoxicity / salsolinol / N-methyl-(R)-salsolinol / 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion / neuroblastoma SH-SY5Y cells / Parkinson's disease / beta-cyclodextrin / HPLC |
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| Research Abstract |
(1) A chromatographic procedure was divised for the quantitative determination of the enantiomers of salsolinol and N-methylsalsolinol, biologically important alkaloids. The enantiomers of salsolinol and N-methylsalsolinol were completely separated using a beta-cyclodextrin bonded column or beta-cyclodextrin as an addict in the mobile phase. The HPLC method was sensitive enough to detect the isoquinolines at the concentration less tha 0.1 pmol per injection. The presence of (R) -and (S) -salsolinol was confirmed in fermented foods and beverages, while N-methylsalsolinol was not detected.
(2) To assert the cytotoxicity quantitatively, a new assay method was devised. Endogenous catechol isoquinolines were examined for the cytotoxicity to human dopaminergic neuroblastoma SH-SY5Y cells, using Alamar Blue assay, an in situ calorimetric measurement of the reduction-oxidation potency. 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion [1,2-DMDHIQ+] was found to be the most potent toxin, and catechol isoquinolines were more toxic than isoquinolines without catechol structure. The results are discussed in relation to the mechanism underlying selective neurotoxicity of endogenous depaminergic neurotoxins.
(3)Dopamine-derived salsolinol and related compounds were examined for their selective neurotoxicity to dopamine neurons by injection into the rat striatum. Among salsolinol analogs examined, only N-methyl-(R)-salsolinol induced behavioral changes very similar to those in Parkinson's disease : hypokinesia.stiff tail, limb twitching at rest and postural abnormality.
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[Publications] Naoi,M.: "Dopamine-derived endogenousl (R) ,2 (N) -dimethyl-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline,N-methyl- (R) -salsolinol,induced parkinsonism in rat : biochemical, pathological and behavioral studies" Brain Research.709. 285-295 (1996)
Description
「研究成果報告書概要(和文)」より
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[Publications] Deng, Y., Maruyama, W., Dostert, P., Takahashi, T., Kawai, M., Naoi, M: "Determination of the (R) -and (S) -enatiomers of salsolinol and N-methylsalsolinol by use of a chiral high performance liquid chromatographic column" Journal of Chromatography B. 670. 47-54 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Deng, Y., Maruyama, W., Kawai, M., Dostert, P., Yamamura, H., Takahashi, T., Naoi, M: "Assay for the (R) -and (S) -enatiomers of salsolinols in biological samples and food with ion-pair high performance liquid chromatography using beta-cyclodextrin as a chiral mobile phase additive." Journal of Chromatography B. (in press). (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takahashi, T., Maruyama, W., Deng, Y., Dostert, P., Nakahara, D,Niwa, T., Ohta, S,Naoi, M: "Cytotoxicity of endogenous isoquinolines to human dopaminergic neuroblastoma SH-SY5Y cells" Journal of Neural Transmission. (in press). (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Naoi, M., Maruyama, W., Dostert, P., Hashizume, Y., Nakahara, D.Takahashi, T., Ota, M: "Dopamine-derived endogenous 1 (R), 2 (N) - dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydro- isoquinoline, N-methyl- (R) -salsolinol, induced parkinsonism in rat : biochemical, pathological and behavioral studies" Brain Research. 709. 285-295 (1996)
Description
「研究成果報告書概要(欧文)」より
