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Tranilast Inhibits TRPV2 and Suppresses Fibrosis Progression and Weight Gain in a NASH Model Mouse.
Nagata, Takahiro; Shakado, Satoshi; Yamauchi, Eri; Tokushige, Hiroaki; Miyayama, Takashi; Yamauchi, Ryo; Fukuda, Hiromi; Fukunaga, Atsushi; Tanaka, Takashi; Takata, Kazuhide; Yokoyama, Keiji; Hirai, Fumihito.
Afiliação
  • Nagata T; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan takahiro1328@hotmail.co.jp.
  • Shakado S; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Yamauchi E; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Tokushige H; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Miyayama T; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Yamauchi R; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Fukuda H; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Fukunaga A; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Tanaka T; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Takata K; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Yokoyama K; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
  • Hirai F; Departments of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Anticancer Res ; 44(8): 3593-3604, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39060042
ABSTRACT
BACKGROUND/

AIM:

This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. MATERIALS AND

METHODS:

C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines.

RESULTS:

Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels.

CONCLUSION:

In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aumento de Peso / Modelos Animais de Doenças / Canais de Cátion TRPV / Ortoaminobenzoatos / Hepatopatia Gordurosa não Alcoólica / Cirrose Hepática Limite: Animals Idioma: En Revista: Anticancer Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Aumento de Peso / Modelos Animais de Doenças / Canais de Cátion TRPV / Ortoaminobenzoatos / Hepatopatia Gordurosa não Alcoólica / Cirrose Hepática Limite: Animals Idioma: En Revista: Anticancer Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão