title: Novel antioxidative nanotherapeutics in a rat periodontitis model: Reactive oxygen species scavenging by redox injectable gel suppresses alveolar bone resorption.
abstract: The excessive production of reactive oxygen species (ROS) has been implicated in a variety of disorders, but to date, ROS scavengers have not been widely used for local treatment of inflammation, because they are rapidly eliminated from the inflamed site. We have designed a novel redox injectable gel (RIG) that is formed at 37 °C after disintegration of nano-assembled flower micelles allowing nitroxide radicals to act locally as specific ROS scavengers for the treatment of periodontitis. In the present study, we have confirmed retention of the RIG in the periodontal region, along with its antioxidant-related anti-inflammatory effects, and we have subsequently evaluated the inhibitory effect of the RIG against Porphyromonas gingivalis (P. gingivalis)-induced alveolar bone loss attributed to ROS. Alveolar bone loss was estimated by morphometry, gingival blood flow was measured using laser Doppler flowmetry, and osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase staining. The results show that the RIG can inhibit P. gingivalis-induced bone loss by antioxidant-related anti-inflammatory actions, and this suggests that the RIG is a promising novel therapeutic agent for the treatment of P. gingivalis-induced periodontitis.
authors.affiliation: Department of Prosthodontics and Oral Rehabilitation, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Saita
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kaneko
authors.affiliation: Department of Microbiology, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Shun-suke
authors.initials: SS
authors.lastname: Takahashi
authors.affiliation: Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Wada-Takahashi
authors.affiliation: Department of Radiopraxis Science, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kawamata
authors.affiliation: Department of Radiopraxis Science, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Yokosuka-shonan Disaster Health Emergency Research Center and ESR Laboratories, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Masaichi-Chang-il
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Nobushiro
authors.initials: N
authors.lastname: Hamada
authors.affiliation: Department of Prosthodontics and Oral Rehabilitation, Graduate School of Dentistry, Kanagawa Dental University, Inaoka 82, Yokosuka, Kanagawa 238-8580, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kimoto
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000539:Alveolar Process / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy*; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D036103:Nanotechnology; D010084:Oxidation-Reduction; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D008315:Malondialdehyde
keywords: Antioxidant; Inflammation; Oxidative stress; Periodontitis; Porphyromonas gingivalis; Reactive oxygen species (ROS)