title: Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on hepatic ischemia/reperfusion injury in mice.
abstract: Reactive oxygen species (ROS) are involved in the pathophysiology of ischemia/reperfusion injury. To protect mouse hepatocytes from ischemia/reperfusion injury, we prepared two different sizes of citric acid-protected platinum nanoparticles (Pt-NPs), which exhibited ROS-scavenging activities and selective delivery to a specific type of liver cell. Small Pt-NPs (30 nm) reduced the superoxide anion, hydrogen peroxide, and hydroxyl radical levels in solution to a greater extent than did large Pt-NPs (106 nm). Large and small Pt-NPs predominantly accumulated in hepatic nonparenchymal cells after intravenous injection into mice. In a mouse model of ischemia/reperfusion injury, in which hepatic injury was induced by occluding the portal vein for 15 min followed by 6 h reperfusion, the increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities was inhibited by a bolus intravenous injection of either large or small Pt-NPs. However, small Pt-NPs inhibited the increase in these markers of hepatic injury to a greater extent than did large Pt-NPs. These results indicate that Pt-NPs can be used to prevent hepatic ischemia/reperfusion injury. To our knowledge, this is the first report demonstrating the pharmacokinetics and efficacy of Pt-NPs to prevent hepatic ischemia/reperfusion injury.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. hkatsumi@mb.kyoto-phu.ac.jp.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fukui
authors.forename: Kanako
authors.initials: K
authors.lastname: Sato
authors.forename: Shoko
authors.initials: S
authors.lastname: Maruyama
authors.forename: Shugo
authors.initials: S
authors.lastname: Yamashita
authors.forename: Erika
authors.initials: E
authors.lastname: Mizumoto
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.forename: Munetaka
authors.initials: M
authors.lastname: Oyama
authors.forename: Masataka
authors.initials: M
authors.lastname: Sano
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D016166:Free Radical Scavengers / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D010984:Platinum / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D014018:Tissue Distribution
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D010984:Platinum