{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:24:20Z","timestamp":1790511860241,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose\u2014<\/jats:title><jats:p>We recently found that acrolein (CH<jats:sub>2<\/jats:sub>=CH-CHO) is more strongly involved in brain infarction compared with reactive oxygen species. In this study, we looked for acrolein scavengers with less side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\u2014<\/jats:title><jats:p>Photochemically induced thrombosis model mice were prepared by injection of Rose Bengal. Effects of<jats:italic>N<\/jats:italic>-acetylcysteine (NAC) derivatives on brain infarction were evaluated using the public domain National Institutes of Health image program.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results\u2014<\/jats:title><jats:p>NAC, NAC ethyl ester, and NAC benzyl ester (150 mg\/kg) were administered intraperitoneally at the time of induction of ischemia, or these NAC derivatives (50 mg\/kg) were administered 3\u00d7 at 24-h intervals before induction of ischemia and 1 more administration at the time of induction of ischemia. The size of brain infarction decreased in the order NAC benzyl ester&gt;NAC ethyl ester&gt;NAC in both experimental conditions. Detoxification of acrolein occurred through conjugation of acrolein with glutathione, which was catalyzed by glutathione<jats:italic>S<\/jats:italic>-transferases, rather than direct conjugation between acrolein and NAC derivatives. The level of glutathione<jats:italic>S<\/jats:italic>-transferases at the locus of brain infarction was in the order of administration of NAC benzyl ester&gt;NAC ethyl ester&gt;NAC&gt;no NAC derivatives, suggesting that NAC derivatives stabilize glutathione<jats:italic>S<\/jats:italic>-transferases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>The results indicate that detoxification of acrolein by NAC derivatives is caused through glutathione conjugation with acrolein catalyzed by glutathione<jats:italic>S<\/jats:italic>-transferases, which can be stabilized by NAC derivatives. This is a new concept of acrolein detoxification by NAC derivatives.<\/jats:p><\/jats:sec>","DOI":"10.1161\/strokeaha.118.021755","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T15:29:53Z","timestamp":1528126193000},"page":"1727-1733","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Protective Effects of Brain Infarction by<i>N<\/i>-Acetylcysteine Derivatives"],"prefix":"10.1161","volume":"49","author":[{"given":"Takeshi","family":"Uemura","sequence":"first","affiliation":[{"name":"From the Amine Pharma Research Institute, Innovation Plaza at Chiba University, Japan (T.U., K.I.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Japan (K.W., K.K., K.H., N.K., M.K., H.T., T.T., 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