Intrahepatic cholestasis induced by α-naphthylisothiocyanate can cause gut-liver axis disorders

Environ Toxicol Pharmacol. 2021 Aug:86:103672. doi: 10.1016/j.etap.2021.103672. Epub 2021 May 11.

Abstract

Clinical studies have shown that Intrahepatic cholestasis is closely related to intestinal injury. The gut-liver axis theory suggests that the intestine and liver are closely related, and that bile acids are important mediators linking the intestine and liver. We compared two cholestasis models: a single injection model that received a single subcutaneous ANIT injection (75 mg/kg), and a multiple subcutaneous injection model that received an injection of ANIT (50 mg/kg) every other day for 2 weeks. We used Transmetil (ademetionine 1,4-butanedisulfonate) to relieve intrahepatic cholestasis in the multiple injection group. In the multiple injection group, we found increased hepatic bile duct hyperplasia, increased fibrosis of the liver, increased small intestine inflammation and oxidative damage, increased harmful bile acids, decreased bile acids transporter levels. After treatment with Transmetil, the liver and gut injuries were relieved. These results suggest that intrahepatic cholestasis can cause disorders of the gut-liver axis.

Keywords: Alpha naphthylisothiocyanate; Cholestasis; Gut-liver axis.

MeSH terms

  • 1-Naphthylisothiocyanate*
  • Animals
  • Bile Acids and Salts / analysis
  • Cholestasis, Intrahepatic / chemically induced*
  • Cholestasis, Intrahepatic / genetics
  • Cholestasis, Intrahepatic / pathology
  • Cytokines / genetics
  • Feces / chemistry
  • Intestinal Diseases / chemically induced*
  • Intestinal Diseases / genetics
  • Intestinal Diseases / pathology
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Intestine, Small / pathology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • Bile Acids and Salts
  • Cytokines
  • 1-Naphthylisothiocyanate