Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

World J Gastroenterol. 2008 Dec 21;14(47):7240-6. doi: 10.3748/wjg.14.7240.

Abstract

Aim: To investigate the effects of rosiglitazone (RGZ) on expression of interleukin-18 (IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease (NAFLD) rats.

Methods: Twenty-eight Sprague-Dawley (SD) rats were randomly divided into control, NAFLD, and RGZ treated NAFLD groups. A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk. The NAFLD animals were treated with RGZ or vehicle for the last 4 wk (week 9-12) and then sacrificed to obtain liver tissues. Histological changes were analyzed with HE, oil red O and Masson's trichrome staining. Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis.

Results: The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group. Steatosis, inflammation and fibrosis, found in the liver of NAFLD rats, were significantly improved 4 wk after RGZ treatment. The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.

Conclusion: RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats. The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Disease Models, Animal
  • Fatty Liver / drug therapy*
  • Fatty Liver / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance
  • Interleukin-18 / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*

Substances

  • Hypoglycemic Agents
  • Interleukin-18
  • Thiazolidinediones
  • Rosiglitazone
  • Caspase 1