Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.

• Material Type: 博士論文
• Title: Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.
• Author/Editor: Ozutsumi, Takahiro; Namisaki, Tadashi; Shimozato, Naotaka; Kaji, Kosuke; Tsuji, Yuki; Kaya, Daisuke; Fujinaga, Yukihisa; Furukawa, Masanori; Nakanishi, Keisuke; Sato, Shinya; Sawada, Yasuhiko; Saikawa, Soichiro; Kitagawa, Koh; Takaya, Hiroaki; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Noguchi, Ryuichi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• Author Heading: Ozutsumi, Takahiro; Namisaki, Tadashi; Shimozato, Naotaka; Kaji, Kosuke; Tsuji, Yuki; Kaya, Daisuke; Fujinaga, Yukihisa; Furukawa, Masanori; Nakanishi, Keisuke; Sato, Shinya; Sawada, Yasuhiko; Saikawa, Soichiro; Kitagawa, Koh; Takaya, Hiroaki; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Noguchi, Ryuichi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• Publication, Distribution, etc.: MDPI
• Publication Date: 2020-03-21
• Publication Date (W3CDTF): 2020-03-21
• Alternative Title: エスジーエルティー2阻害薬（カナグリフロジン）およびジペプチジルペプチダーゼ４阻害薬（テネリグリプチン）との併用療法は非糖尿病ラットモデルにおける非アルコール性脂肪肝炎の進行を抑制する
• Periodical title: International journal of molecular sciences
• No. or year of volume/issue: 21 6
• Volume: 21
• Issue: 6
• Pages: Article No.2164-
• ISSN (Periodical Title): ISSN : 1422-0067
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2021-03-15
• Dissertation Number: 甲第765号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: non-alcoholic steatohepatitis; hepatic fibrogenesis; hepatocarcinogenesis; canagliflozin; teneligliptin
• Target Audience: 一般
• Note (General): type:Thesis; Hepatocellular carcinoma (HCC) is the strongest independent predictor of mortality in non-alcoholic steatohepatitis (NASH)-related cirrhosis. The effects and mechanisms of combination of sodium-dependent glucose cotransporter inhibitor and canagliflozin (CA) and dipeptidyl peptidase-4 inhibitor and teneligliptin (TE) on non-diabetic NASH progression were examined. CA and TE suppressed choline-deficient, L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. CA alone or with TE significantly decreased proinflammatory cytokine expression. CA and TE significantly attenuated hepatic lipid peroxidation. In vitro studies showed that TE alone or with CA inhibited cell proliferation and TGF-β1 and α1 (I)-procollagen mRNA expression in Ac-HSCs. CA+TE inhibited liver fibrogenesis by attenuating hepatic lipid peroxidation and inflammation and by inhibiting Ac-HSC proliferation with concomitant attenuation of hepatic lipid peroxidation. Moreover, CA+TE suppressed in vivo angiogenesis and oxidative DNA damage. CA or CA+TE inhibited HCC cells and human umbilical vein endothelial cell (HUVEC) proliferation. CA+TE suppressed vascular endothelial growth factor expression and promoted increased E-cadherin expression in HUVECs. CA+TE potentially exerts synergistic effects on hepatocarcinogenesis prevention by suppressing HCC cell proliferation and angiogenesis and concomitantly reducing oxidative stress and by inhibiting angiogenesis with attenuation of oxidative stress. CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH.; 博士（医学）・甲第765号・令和3年3月15日; © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:International journal of molecular sciences Vol.21 No.6 Article No.2164 (2020 Mar); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3889; identifier:International journal of molecular sciences, 21(6): Article No.2164
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.3390/ijms21062164
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/1/01%e7%94%b2765%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/2/02%e7%94%b2765%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3889/3/02%e7%94%b2765%e6%9c%ac%e6%96%87.pdf fulltext