title: Adsorption of histones on natural polysaccharides: The potential as agent for multiple organ failure in sepsis.
abstract: Histones are intracellular proteins that are structural elements of nuclear chromatin and regulate gene transcription. However, the extracellular histones released in response to bacterial challenges have been identified as mediators contributing to endothelial dysfunction, organ failure, and death during sepsis. In the present study, the adsorption of histones as well as plasma proteins (α1-acid glycoprotein (AGP), albumin, and γ-globulin) on alginic acid, pectin, dextran, and chitosan was examined in order to evaluate the potential of natural polysaccharides as therapeutic agents for multiple organ failure in sepsis. Alginic acid and pectin strongly adsorbed histones, whereas the adsorption abilities of dextran and chitosan toward histones were very low or negligible. Among the natural polysaccharides examined, only alginic acid did not adsorb any of the plasma proteins. These results demonstrated that alginic acid strongly adsorbed histones, but not plasma proteins; therefore, it has potential as a candidate drug for the treatment of multiple organ failure in sepsis.
authors.affiliation: Department of Biochemical Toxicology, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan. Electronic address: t-isobe@hamayaku.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kofuji
authors.affiliation: Department of Clinical Pharmacy, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Clinical Pharmacy, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimori
authors.affiliation: Department of Clinical Pharmacy, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Clinical Pharmacy, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shigeyama
authors.affiliation: Department of Biochemical Toxicology, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan.
authors.forename: Nobumitsu
authors.initials: N
authors.lastname: Hanioka
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Murata
mesh_terms: D000327:Adsorption; D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology; D018805:Sepsis / Q000150:complications / Q000188:drug therapy
chemical_list: D000464:Alginates; D001688:Biological Products; D001798:Blood Proteins; D006603:Hexuronic Acids; D006657:Histones; D011134:Polysaccharides; D020723:Glucuronic Acid
keywords: Alginic acid; Histones; Multiple organ failure; Natural polysaccharides; Pectin; Sepsis