In vivo/in vitro evaluation of antioxidant activity of drugs for lifestyle disease.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20790400
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Kumamoto University
• Principal Investigator: KADOWAKI Daisuke Kumamoto University, 薬学部, 講師 (70433000)
• Project Period (FY): 2008 – 2010
• Keywords: 酸化ストレス / 生活習慣病 / 降圧薬 / 慢性腎臓病

Research Abstract

Angiotensin II type 1 (AT1) receptor blockers (ARBs) inhibit the renin-angiotensinaldosterone system (RAAS) and have been shown to be effective for treating hypertension. Recently, apart from their ability to lower blood pressure (BP), ARBs had also been reported to show protective effects in cardiovascular and renal diseases. Antioxidant activity is thought to be one of the most important protective effects and several mechanisms have been proposed in the in vitro studies. However, the antioxidant effect of olmesartan has not been extensively examined in the in vivo studies. Therefore, the aim of this study was to examine the antioxidant activity of olmesartan by utilizing oxidized albumin, a sensitive marker of oxidative stress, in the in vivo and in vitro evaluation systems. As a result, olmesartan effectively lowered the extent of oxidative damage to albumin in the in vitro and the in vivo studies. The antioxidant activity of olmesartan is greatly related to its renoprotective effects but not its antihypertensive effect. It is possible that the direct and indirect antioxidant effect of olmesartan is due to its common core structure through modulation of NADPH oxidase activity. Therefore, the potential indication of olmesartan as an antioxidant drug in addition to its antihypertensive effect should be explored. These results are important for developing a new ARB, which has a great protective effect in cardiovascular and renal diseases.

Research Products

• [Journal Article] Spectroscopic studies of interactions of chondroitin sulfates with cisplatin. (2011)
  • Author(s): Zhang JS, Anraku M, Kadowaki D, Imai T, Suenaga A, Odani A, Otagiri M.
  • Journal Title: Carbohydr Res. 346 Pages: 631-637
  • Peer Reviewed
• [Journal Article] Fluid resuscitation with hemoglobin-vesicles prevents Escherichia coli growth via complement activation in a hemorrhagic shock rat model. (2011)
  • Author(s): Taguchi K, Ogaki S, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
  • Journal Title: J Pharmacol Exp Ther. 337 Pages: 201-208
  • Peer Reviewed
• [Journal Article] Repeated injection of high doses of hemoglobin encapsulated liposomes (hemoglobin-vesicles) induces accelerated blood clearance in a hemorrhagic shock rat model. (2011)
  • Author(s): Taguchi K, Iwao Y, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
  • Journal Title: Drug Metab Dispos. 39 Pages: 484-489
  • Peer Reviewed
• [Journal Article] Antioxidant properties of high molecular weight dietary chitosan in vitro and in vivo. (2011)
  • Author(s): Anraku M, Fujii T, Kondo Y, Kojima E, Hata T, Tabuchi N, Tsuchiya D, Goromaru T, Tsutsumi H, Kadowaki D, Maruyama T, Otagiri M, Tomida H.
  • Journal Title: Carbohydrate Polymers. 83 Pages: 501-505
  • Peer Reviewed
• [Journal Article] Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment. (2010)
  • Author(s): Taguchi K, Miyasato M, Ujihira H, Watanabe H, Kadowaki D, Sakai H, Tsuchida E, Horinouchi H, Kobayashi K, Maruyama T, Otagiri M.
  • Journal Title: Toxicology and Applied Pharmacology. 248 Pages: 234-241
  • Peer Reviewed
• [Journal Article] The uremic solute indoxyl sulfate acts as an antioxidant against superoxide anion radicals under normal-physiological conditions. (2010)
  • Author(s): Miyamoto Y, Iwao Y, Tasaki Y, Sato K, Ishima Y, Watanabe H, Kadowaki D, Maruyama T, Otagiri M.
  • Journal Title: FEBS Lett. 584 Pages: 2816-2820
  • Peer Reviewed
• [Journal Article] Construction of an Expression System for Human α1-Acid Glycoprotein in E.coli : the Role of Oligosaccharide Moieties on Structural and Functional Properties. (2010)
  • Author(s): Nishi K, Fukunaga N, Ono T, Akuta T, Yumita N, Watanabe H, Kadowaki D, Suenaga A, Maruyama T, Otagiri M.
  • Journal Title: Drug Metabolism and Pharmacokinetics. 25 Pages: 200-207
  • Peer Reviewed
• [Journal Article] Receptor-mediated uptake of human α1-acid glycoprotein into liver parenchymal cells in mice. (2010)
  • Author(s): Matsumoto K, Nishi K, Kikuchi M, Watanabe H, Nakajou K, Komori H, Kadowaki D, Suenaga A, Maruyama T, Otagiri M.
  • Journal Title: Drug Metabolism and Pharmacokinetics. 25 Pages: 101-107
  • Peer Reviewed
• [Journal Article] Improvement of hyperphosphatemia following patient education. (2009)
  • Author(s): Satoh M, Koizumi A, Izumi S, Kugoh Y, Kiriyama E, Oguma E, Furukubo T, Matsunaga, C, Yamakawa T, Kadowaki D, Hirata S.
  • Journal Title: the Journal of Pharmacy Technology. 25 Pages: 3-9
  • Peer Reviewed
• [Journal Article] Antioxidant effects of a dietary supplement : reduction of indices of oxidative stress in normal subjects by water-soluble chitosan. (2009)
  • Author(s): Anraku M, Fujii T, Furutani N, Kadowaki D, Maruyama T, Otagiri M, Gebicki JM, Tomida H.
  • Journal Title: Food and Chemical Toxicology. 47 Pages: 104-109
  • Peer Reviewed
• [Journal Article] A site-directed mutagenesis study of drug-binding selectivity in genetic variants of human α1-acid glycoprotein. (2009)
  • Author(s): Nishi K, Ueno M, Murakami Y, Fukunaga N, Akuta T, Kadowaki D, Watanabe H, Suenaga A, Maruyama T, Otagiri M.
  • Journal Title: Journal of Pharmaceutical Sciences. 98 Pages: 4316-4326
  • Peer Reviewed
• [Journal Article] Hemoglobin vesicles, polyethylene glycol (PEG)ylated liposomes developed as a red blood cell substitute, do not induce the accelerated blood clearance phenomenon in mice. (2009)
  • Author(s): Taguchi K, Urata Y, Anraku M, Watanabe H, Kadowaki D, Sakai H, Horinouchi H, Kobayashi K, Tsuchida E, Maruyama T, Otagiri M.
  • Journal Title: Drug Metabolism and Disposition. 37 Pages: 2197-2203
  • Peer Reviewed
• [Journal Article] Evaluation for antioxidant and renoprotective activity of olmesartan using nephrectomy rats. (2009)
  • Author(s): Kadowaki D, Anraku M, Tasaki Y, Taguchi K, Shimoishi K, Seo H, Hirata S, Maruyama T, Otagiri M.
  • Journal Title: Biological & Pharmaceutical Bulletin. 32 Pages: 2041-2045
  • Peer Reviewed
• [Journal Article] To facilitate the compliance of phosphate binder for the control of hyperphosphatemia in chronic kidney disease patients. (2009)
  • Author(s): Maruyama T, Kadowaki D.
  • Journal Title: Clinical Calcium. 19 Pages: 248-252
  • Peer Reviewed
• [Presentation] 高尿酸血症治療薬ベンズブロマロンの抗酸化作用評価 (2011)
  • Author(s): 坂口翔一, 宮本洋平, 佐藤圭創, 丸山徹, 小田切優樹, 平田純生, 門脇大介
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: グランシップ静岡, 静岡
  • Year and Date: 2011-03-29
• [Presentation] Relationship between Antioxidant and Renoprotective Activity of Olmesartan (2010)
  • Author(s): Daisuke Kadowaki, Makoto Anraku, Yuka Tasaki, Kazuaki Taguchi, Kazuki Shimoishi, Ayaka Suenaga, Hiroshi Watanabe, Hakaru Seo, Sumio Hirata, Toru Maruyama, Masaki Otagiri
  • Organizer: 70th FIP WORLD CONGRESS OF PHARMACY AND PHARMACEUTICAL SCIENCES
  • Place of Presentation: Lisboa Congress Center, Portugal
  • Year and Date: 2010-08-28
• [Presentation] アセトアミノフェンがCRFモデルラットの腎機能に及ぼす影響と投与量の関係 (2010)
  • Author(s): 門脇大介, 済川聡美, 長嶋美里, 成田勇樹, 曽田彩夏, 平田純生
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2010-06-16
• [Presentation] 腎排泄型薬剤の持参薬に関する多施設実態調査 (2009)
  • Author(s): 浦田由紀乃, 門脇大介, 柴田啓智, 下石和樹, 森直樹, 山室蕗子, 宮村重幸
  • Organizer: 第19回日本医療薬学会年会
  • Place of Presentation: 長崎ブリックホール, 長崎
  • Year and Date: 2009-10-24
• [Presentation] EVALUATION FOR ANTIOXIDANT AND RENOPROTECTIVE ACTIVITY OF OLMESARTAN USING NEPHRECTOMY RATS (2009)
  • Author(s): Daisuke Kadowaki, Makoto Anraku, Yuka Tasaki, Kazuaki Taguchi, Kazuki Shimoishi, Ayaka Suenaga, Hiroshi Watanabe, Sumio Hirata, Toru Maruyama, Masaki Otagiri
  • Organizer: AFPS 2009
  • Place of Presentation: Centennial Hall Kyushu University School of Medicine, Fukuoka
  • Year and Date: 2009-10-15
• [Presentation] RA系阻害薬の腎保護効果 (2008)
  • Author(s): 門脇大介
  • Organizer: 第2回日本腎と薬剤研究会
  • Place of Presentation: 熊本市民会館, 熊本(招待講演)
  • Year and Date: 2008-12-06
• [Presentation] IN VIVO EVALUATION OF ANTIOXIDANT ACTIVITY OF OLMESARTAN UTILIZING OXIDIZED ALBUMIN (2008)
  • Author(s): Daisuke Kadowaki, Makoto Anraku, Yuka Tasaki, Kazuaki Taguchi, Kenichiro Kitamura, Kazuki Shimoishi, Toru Maruyama, Masaki Otagiri
  • Organizer: The 23rd JSSX Annual Meeting
  • Place of Presentation: 熊本市民会館, 熊本
  • Year and Date: 2008-10-30
• [Presentation] 慢性腎臓病における包括的な抗酸化治療戦略 (2008)
  • Author(s): 丸山徹, 門脇大介, 下石和樹, 小田切優樹
  • Organizer: 医療薬学フォーラム2008
  • Place of Presentation: タワーホール船堀, 東京
  • Year and Date: 2008-07-13
• [Presentation] 腎不全患者への薬物適正使用を目指して-不眠に対する薬物の使い方- (2008)
  • Author(s): 門脇大介, 平田純生
  • Organizer: 第53回日本透析医学会
  • Place of Presentation: 神戸コンベンションセンター, 神戸(招待講演)
  • Year and Date: 2008-06-22
• [Book] CKDの治療と薬Q&A (2010)
  • Author(s): 門脇大介
  • Total Pages: 128
  • Publisher: じほう
• [Book] 透析ケア冬季増刊号ナースが知りたい透析患者のくすりQ&A64 (2009)
  • Author(s): 門脇大介
  • Total Pages: 40-43
  • Publisher: メディカ出版
• [Book] 腎不全ハンドブック-CKDから先端透析療法:up to date (2009)
  • Author(s): 門脇大介, 平田純生
  • Total Pages: 99-103
  • Publisher: 医薬ジャーナル社