Protective Effects of Ipragliflozin, a Sodium-glucose Cotransporter 2 Inhibitor, on a Non-alcoholic Steatohepatitis Mouse Model

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  • Yamane Masafumi
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Matono Tomomitsu
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Okano Jun-ichi
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Nagahara Ran
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Matsuki Yukako
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Okamoto Toshiaki
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Miyoshi Ken-ichi
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Sugihara Takaaki
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Nagahara Takakazu
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
  • Koda Masahiko
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan †Hino Hospital, Hino-cho 689-4504, Japan
  • Isomoto Hajime
    *Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan

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Abstract

<p>Background The options for the treatment of nonalcoholic steatohepatitis (NASH) are limited. We examined the effects of ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, on the fatty liver Shionogi (FLS)-ob/ob mice, a non-alcoholic steatohepatitis mouse model.</p><p>Methods FLS-ob/ob male mice were treated with vehicle (n = 10) and ipragliflozin (n = 8). Serum metabolic markers, histopathology of the liver, hepatic cholesterol and triglyceride levels and hepatic mRNA levels related to fibrosis, lipid metabolism and endoplasmic reticulum (ER) stress were compared between the two groups.</p><p>Results The body weight and hepatic cholesterol and triglyceride levels were significantly decreased in the ipragliflozin group compared with the control group. Hepatic steatosis and fibrosis were significantly ameliorated by the treatment with ipragliflozin. Hepatic infiltration of macrophage, expression levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and hepatic mRNA levels of ER stress markers were not significantly modulated by the treatment with ipragliflozin.</p><p>Conclusion Ipragliflozin can be a therapeutic option for patients with NASH. The precise mechanisms of action need to be clarified in future studies.</p>

Journal

  • Yonago Acta Medica

    Yonago Acta Medica 62 (1), 030-035, 2019

    Tottori University Medical Press

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