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Stereospecific cardiotoxicity evaluation of local anesthetics using their discriminable interactions with biomimetic chiral membranes
https://asahi-u.repo.nii.ac.jp/records/1504
https://asahi-u.repo.nii.ac.jp/records/15045c50e954-d8cc-42d3-a79a-234c502952e9
| Item type | 朝日大学 教育・研究業績(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-02-10 | |||||
| タイトル | ||||||
| タイトル | Stereospecific cardiotoxicity evaluation of local anesthetics using their discriminable interactions with biomimetic chiral membranes | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_1843 | |||||
| 資源タイプ | other | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 業績分類 | ||||||
| 値 | 学会発表 | |||||
| 教員氏名 |
土屋, 博紀
× 土屋, 博紀 |
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| 発行、発表雑誌等、又は発表学会等の名称 | ||||||
| 値 | the 49th Congress of the European Societies of Toxicology EUROTOX 2013, Interlaken (Switzerland) | |||||
| 巻 | ||||||
| 値 | Toxicology Letters, 221S: S95 (2013) | |||||
| 単著、共著の別 | ||||||
| 値 | 共著 | |||||
| 発行又は発表の年月 | ||||||
| 日付 | 2013-09 | |||||
| ISSN | ||||||
| 値 | 0378-4274 | |||||
| 概要 | ||||||
| 値 | One enantiomer is preferred over its antipode and racemate to reduce drug toxicity. Apart from drug-target proteins, it has been reported that membrane lipids are responsible for the stereostructure-dependent effects of drugs. We compared the membrane interactions of local anesthetics to evaluate their stereospecific cardiotoxicities and get a novel clue to less toxic drugs. Bupivacaine and ropivacaine (S(–)-, racemic and R(+)-) were reacted at cardiotoxically-relevant concentrations with biomimetic membranes which were prepared with different phospholipids and steroids, followed by measuring fluorescence polarization to determine the drug-membrane interactions. All drugs acted on lipid bilayers to change the membrane physicochemical property as one of cardiotoxic mechanisms. The membranes consisting of phospholipids alone failed to discriminate between anesthetic stereoisomers. When increasing its membrane composition to 40 mol%, cholesterol with several chiral centers caused the enantioselective membrane interactions of bupivacaine and ropivacaine with the potency being R(+)-enantiomer > racemate > S(–)-enantiomer, which agreed with their stereospecific cardiotoxicities. 5α-Cholestan-3β-ol produced the same difference to be R(+)- > racemic > S(–)-bupivacaine, whereas 5β-cholestan-3α-ol showed the reversed rank order to be S(–)- > racemic > R(+)-bupivacaine. Neither membranes containing 5α-cholestan-3β-ol and 5β-cholestan-3α-ol (50:50, mol%) nor membranes without containing chiral steroids discriminated between bupivacaine stereoisomers. The opposite configuration allows drug stereoisomers to be discriminated by enantioselectively interacting with chiral lipid membranes. The comparative membrane interactions of drugs are correlated with their stereospecific cardiotoxicities, suggesting that S(–)-enantiomers should be clinically used to reduce the toxic effects of local anesthetics. | |||||
