| Project/Area Number |
10672142
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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 |
応用薬理学・医療系薬学
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
MATSUBARA Kazuo Asahikawa Medical College, Professor, 医学部, 教授 (20127533)
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| Co-Investigator(Kenkyū-buntansha) |
UEZONO Takashi ASAHIKAWA MEDICAL COLLEGE, INSTRUCTOR, 医学部, 助手 (70294387)
SHIMIZU Keiko ASAHIKAWA MEDICAL COLLEGE, INSTRUCTOR, 医学部, 助手 (90312462)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Paraguat / Cefoselis / Blood-brain barrier / Brain microdialysis / Aminoacid transporter / Renal dysfunction / パラコート / 薬物 / 加齢 / 能動輸送系 |
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| Research Abstract |
1 . Blood-brain barrier penetration of paraquat
Blood-brain barrier (BBB) penetration of paraquat has not been well documented. In this study, we examined the mamler in the BBB penetration of paraquat using a brain microdialysis technique in rats. After subcutaneous administration, paraquat appeared dose-dependently in the dialysate. On the contrary, MPP+ could not penetrate the BBB in either control or paraquat pretreated rats . This indicated that the penetration of paraquat into the brain would be mediated by a certain carrier process, but not resulted from the destruction of the BBB. To test if paraquat was carried through the BBB on the a certain amino acid transporter, valine or lysine was pretreated. We found that valine strikingly reduced the BBB penetration of paraquat and elevated blood levels. Thus paraquat is possibly taken up into the brain by the neutral amino acid transport system. However, it is not certain whether the exposure to paraquat for a long period induces brain damage.
2. Blood-brain barrier penetration of cefoselis in renal dysfunctional rats
Cefoselis is β-lactam antibiotics and often causes side effects associated with central nervous system in renal dysfunction and senior patients. There is no available data of the BBB penetration of cefoselis. Thus, we studied the BBB penetration of cefoselis in rats using the brain microdialysis technique. Renal dysfunction rats were prepared by an iv injection of uranyl nitrate. After an iv administration, cefoselis appeared dose-dependently in the dialysate. The ratio of blood to brain cefoselis concentration was relatively high. In renal dysfunction rats, the disappearance of cefoselis from brain exratcellular fluid was strikingly delayed. This would cause side effects of cefoselis associated with central nervous system.
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