{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:39:04Z","timestamp":1792147144785,"version":"4.4.0"},"reference-count":70,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H02871"],"award-info":[{"award-number":["JP20H02871"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["JP21K20543"],"award-info":[{"award-number":["JP21K20543"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","award":["202120130"],"award-info":[{"award-number":["202120130"]}],"id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22ym0126814j0001"],"award-info":[{"award-number":["22ym0126814j0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,28]]},"abstract":"<jats:p>\n                    Simultaneous poisoning by carbon monoxide (CO) and hydrogen cyanide is the major cause of mortality in fire gas accidents. Here, we report on the invention of an injectable antidote against CO and cyanide (CN\n                    <jats:sup>\u2013<\/jats:sup>\n                    ) mixed poisoning. The solution contains four compounds: iron(III)porphyrin (Fe\n                    <jats:sup>III<\/jats:sup>\n                    TPPS, F), two methyl-\u03b2-cyclodextrin (CD) dimers linked by pyridine (Py3CD, P) and imidazole (Im3CD, I), and a reducing agent (Na\n                    <jats:sub>2<\/jats:sub>\n                    S\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    , S). When these compounds are dissolved in saline, the solution contains two synthetic heme models including a complex of F with P (hemoCD-P) and another one of F with I (hemoCD-I), both in their iron(II) state. hemoCD-P is stable in its iron(II) state and captures CO more strongly than native hemoproteins, while hemoCD-I is readily autoxidized to its iron(III) state to scavenge CN\n                    <jats:sup>\u2013<\/jats:sup>\n                    once injected into blood circulation. The mixed solution (hemoCD-Twins) exhibited remarkable protective effects against acute CO and CN\n                    <jats:sup>\u2013<\/jats:sup>\n                    mixed poisoning in mice (~85% survival vs. 0% controls). In a model using rats, exposure to CO and CN\n                    <jats:sup>\u2013<\/jats:sup>\n                    resulted in a significant decrease in heart rate and blood pressure, which were restored by hemoCD-Twins in association with decreased CO and CN\n                    <jats:sup>\u2013<\/jats:sup>\n                    levels in blood. Pharmacokinetic data revealed a fast urinary excretion of hemoCD-Twins with an elimination half-life of 47 min. Finally, to simulate a fire accident and translate our findings to a real-life scenario, we confirmed that combustion gas from acrylic cloth caused severe toxicity to mice and that injection of hemoCD-Twins significantly improved the survival rate, leading to a rapid recovery from the physical incapacitation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2209924120","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T13:58:31Z","timestamp":1676987911000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning"],"prefix":"10.1073","volume":"120","author":[{"given":"Qiyue","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-6750","authenticated-orcid":false,"given":"Xuansu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Fire Engineering, Building Research Institute, Tsukuba, Ibaraki 305-0802, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7772-9367","authenticated-orcid":false,"given":"Akiko","family":"Kiriyama","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science, Doshisha Women\u2019s College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Negi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science, Doshisha Women\u2019s College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Tsukuba Building Research and Testing Laboratory, Center for Better Living, Tsukuba, Ibaraki 305-0802, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Architecture, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-7888","authenticated-orcid":false,"given":"Akira T.","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Innovative Medical Science Tokai University, Isehara, Kanagawa 259-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-2612","authenticated-orcid":false,"given":"Roberto","family":"Motterlini","sequence":"additional","affiliation":[{"name":"University Paris Est Creteil, INSERM, Institut Mondor de Recherche Biom\u00e9dicale (IMRB), Creteil F-94010, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-7937","authenticated-orcid":false,"given":"Roberta","family":"Foresti","sequence":"additional","affiliation":[{"name":"University Paris Est Creteil, INSERM, Institut Mondor de Recherche Biom\u00e9dicale (IMRB), Creteil F-94010, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-7217","authenticated-orcid":false,"given":"Hiroaki","family":"Kitagishi","sequence":"additional","affiliation":[{"name":"Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"M. 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