Scholarlink

<p>The Western diets (WD) induced metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major clinical burden. No pharmacological agent has been approved to treat MAFLD-induced liver cancer and systemic symptoms. In this study, mice were fed a WD combined with a CCl<sub>4</sub> injection for 24 weeks to induce steatohepatitis, fibrosis, and liver cancer. The molecular and therapeutic effects of barbituric acid derivative pyrimidinetrione benzodioxol (BA-5) were evaluated. BA-5 treatment decreased lipids accumulation and inflammatory response through upregulating beta-oxidation genes. Furthermore, WD+CCl<sub>4</sub>-impaired detoxification and antioxidant genes were restored by BA-5. During fibrogenesis, BA-5 treatment reduced the collagen deposition in WD+CCl<sub>4</sub> exposed mice. At the stage of hepatocarcinogenesis, BA-5 blocked the AKT/rpS6-mediated proliferation and reduced HCC markers. Notably, WD-induced anxiety- and depression-like behaviors were significantly improved in BA-5-treated mice. Although delayed BA-5 treatment showed a modest therapeutic effect, early BA-5 intervention serves as a promising agent for addressing metabolic deterioration-induced liver tumorigenesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pyrimidinetrione benzodioxol ameliorates MAFLD-induced liver tumorigenesis and mood disorders in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月3日

查看全文
  • Fang-Yu Hsu,
  • Wan-Chun Chiu,
  • Fat-Moon Suk,
  • Chun-Ya Lee,
  • Ming-Hua Hsu,
  • Yi-Jen Liao

摘要

The Western diets (WD) induced metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major clinical burden. No pharmacological agent has been approved to treat MAFLD-induced liver cancer and systemic symptoms. In this study, mice were fed a WD combined with a CCl4 injection for 24 weeks to induce steatohepatitis, fibrosis, and liver cancer. The molecular and therapeutic effects of barbituric acid derivative pyrimidinetrione benzodioxol (BA-5) were evaluated. BA-5 treatment decreased lipids accumulation and inflammatory response through upregulating beta-oxidation genes. Furthermore, WD+CCl4-impaired detoxification and antioxidant genes were restored by BA-5. During fibrogenesis, BA-5 treatment reduced the collagen deposition in WD+CCl4 exposed mice. At the stage of hepatocarcinogenesis, BA-5 blocked the AKT/rpS6-mediated proliferation and reduced HCC markers. Notably, WD-induced anxiety- and depression-like behaviors were significantly improved in BA-5-treated mice. Although delayed BA-5 treatment showed a modest therapeutic effect, early BA-5 intervention serves as a promising agent for addressing metabolic deterioration-induced liver tumorigenesis.