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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3889

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.
Other Titles: 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
Authors: 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
Keywords: non-alcoholic steatohepatitis
hepatic fibrogenesis
hepatocarcinogenesis
canagliflozin
teneligliptin
Issue Date: 21-Mar-2020
Publisher: MDPI
Citation: International journal of molecular sciences Vol.21 No.6 Article No.2164 (2020 Mar)
Abstract: 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.
Description: 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/).
URI: http://hdl.handle.net/10564/3889
ISSN: 14220067
Academic Degrees and number: 24601A765
Degree-granting date: 2021-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2020年度

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