Strategy for protection of kidney injury based on functioal relation betwee renal specific stress response mechanisms and xenobiotic detoxication systems

2008 Fiscal Year Final Research Report

• Project/Area Number: 17390158
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kumamoto University
• Principal Investigator: SAITO Hideyuki Kumamoto University, 医学部附属病院, 教授 (40225727)
• Co-Investigator(Kenkyū-buntansha): HAMADA Akinobu 熊本大学, 医学部附属病院, 准教授 (00322313) ; WATANABE Hiroshi 熊本大学, 薬学部, 講師 (70398220)
• Co-Investigator(Renkei-kenkyūsha): NONOGUCHI Hiroshi 熊本大学, 大学院・医学薬学研究部, 准教授 (30218341)
• Project Period (FY): 2005 – 2008
• Keywords: 急性腎障害 / 薬剤性腎障害 / 薬物トランスポータ / 抗癌薬 / 腎尿細管

Research Abstract

虚血再灌流及び白金系抗癌薬誘発急性腎不全モデルラットにおいて、低酸素誘導因子の上昇に伴い腎近位尿細管上皮細胞に局在する有機アニオントランスポータおよび有機カチオントランスポータの発現・輸送機能が減少し、尿毒症物質やイオン型薬物の体内動態が著明に変動することを明らかにした。さらに、尿毒症物質の一つであるインドキシル硫酸がこれらトランスポータの発現変動並びに腎障害の進展に密接に関与することを突き止めた。

Research Products

• [Journal Article] Effects of oral administration of S-1 on the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer (2009)
  • Author(s): Yokoo K, Hamada A, Tazoe K, Sasaki Y, Saito H.
  • Journal Title: Ther Drug Monit (in press)
  • Peer Reviewed
• [Journal Article] Constitutive overexpression of P-glycoprotein, rather than breast cancer resistance protein or organic cation transporter 1, contributes to acquisition of imatinib-resistance in K562 cells (2009)
  • Author(s): Hirayama C, Watanabe H, Nakashima R, Nanbu T, Hamada A, Kuniyasu A, Nakayama H, Kawaguchi T, Saito H.
  • Journal Title: Pharm Res. 25 Pages: 827-835
  • Peer Reviewed
• [Journal Article] Regulation of renal organic ion transporters in cisplatin-induced acute kidney injury and uremia in rats (2008)
  • Author(s): Morisaki T, Matsuzaki T, Yokoo K, Kusumoto M, Iwata K, Hamada A, Saito H
  • Journal Title: Pharm Res. 25 Pages: 2526-2533
  • Peer Reviewed
• [Journal Article] Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rOCT2 (Slc22a2)and rMATE1 (Slc47a1)in ischemia/reperfusioninduced acute kidney injury (2008)
  • Author(s): Matsuzaki T, Morisaki T, Sugimoto W, Yokoo K, Sato D, Nonoguchi H, Tomita K, Terada T, Inui K, Hamada A, Saito H.
  • Journal Title: Drug Metab Dispos 36 Pages: 649-654
  • Peer Reviewed
• [Journal Article] Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human A549 lung adenocarcinoma cells (2008)
  • Author(s): Hira A, Watanabe H, Maeda Y, Yokoo K, Sanematsu E, Fujii J, Sasaki JI, Hamada A, Saito H.
  • Journal Title: Biochem Pharmacol 75 Pages: 973-980
  • Peer Reviewed
• [Journal Article] Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute renal failure (2007)
  • Author(s): Matsuzaki T, Watanabe H, Yoshitome K, Morisaki T, Hamada A, Nonoguchi H, Kohda Y, Tomita K, Inui K, Saito H
  • Journal Title: Kidney Int. 71 Pages: 539-547
  • Peer Reviewed
• [Journal Article] Involvement of indoxyl sulfate in renal and central nervous system toxicities during cisplatin-induced acute renal failure (2007)
  • Author(s): Iwata K, Matsuzaki T, Watanabe H, Morisaki T, Ohmura T, Hamada A, SaitoH.
  • Journal Title: Pharm Res. 24 Pages: 662-671
  • Peer Reviewed
• [Presentation] Indoxyl sulfate is involved in the down-regulation of renal organic anion transporter OAT3 under ischemia/reperfusion-induced acute kidney injury (2008)
  • Author(s): Saito H. et.al.
  • Organizer: The 41^<st> Annual Meeting of American Society of Nephrology
  • Place of Presentation: フィラデルフィア
  • Year and Date: 2008-11-07
• [Presentation] Pathophysiological regulation of Slc22A organic anion transporters in cisplatin-induced acute kidney injury and uremia in rats (2008)
  • Author(s): Yokoo K. et.al.
  • Organizer: The 41^<st> Annual Meeting of American Society of Nephrology,
  • Place of Presentation: フィラデルフィア
  • Year and Date: 2008-11-07
• [Presentation] シスプラチン誘発急性腎障害ラットにおける有機イオントランスポータ(Slc22A)ファミリーの発現・機能制御とファモチジン動態変動との関連 (2007)
  • Author(s): 森崎崇文ら
  • Organizer: 第30 回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-11-26
• [Presentation] Down-regulation of organic ion transporter (Slc22A)family members by ischemia/ reperfusion-induced acute renal failure (2007)
  • Author(s): Saito H. et.al.
  • Organizer: The 40^<th> Annual Meeting of American Society of Nephrology
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-11-01
• [Presentation] 虚血再灌流・急性腎不全ラットにおける有機アニオントランスポータrOAT1 及びrOAT3 の発現変動解析 (2006)
  • Author(s): 松崎尊信ら
  • Organizer: 第21 回日本薬物動態学会年会
  • Place of Presentation: 東京
  • Year and Date: 2006-11-30