Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1β, and IL-18 in rat liver

Int Immunopharmacol. 2020 Sep;86:106730. doi: 10.1016/j.intimp.2020.106730. Epub 2020 Jun 26.

Abstract

Non-alcoholic fatty liver (NAFLD) is accompanied by an increased expression of oxidative stress parameters, in addition to the inflammatory cytokines; tumor necrosis factor alpha (TNF-α), interleukin type 1beta (IL-1β), and interleukin type 18 (IL-18). The aim of this study is to investigate the effect of dapagliflizon (DAPA) on high carbohydrate-high fat (HCHF) diet-induced expression of inflammatory cytokines in rat liver. NAFLD was induced by feeding the rats HCHF diet (consist of animal fat tallow and standard show pellets) and the consumption of fructose in drinking water (10%) for 12 or 18 weeks. The oral administration of DAPA (1 mg/kg/day) from 13th week to 18th week significantly improved NAFLD as indicated by a significant reduction in liver aminotransferases in addition to a significant decrease of serum MDA, cholesterol, triglyceride and LDL-cholesterol with concomitant significant elevation of HDL-cholesterol. DAPA-treated animals showed a significant reduction of liver homogenate content of TNF-α, IL-1β, and IL-18. These results indicate that the administration of DAPA may be beneficial against HCHF diet-induced NAFLD. Histopathological examination of liver specimens supported the conclusion that DAPA improves steatohepatitis induced by HCHF diet.

Keywords: Dapagliflozin; HC-HF diet; IL-18; IL-1β; TNF-α.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzhydryl Compounds / therapeutic use*
  • Diet
  • Fatty Liver / metabolism*
  • Fructose / metabolism
  • Glucosides / therapeutic use*
  • Humans
  • Inflammation / immunology*
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Rats
  • Rats, Wistar
  • Transaminases / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzhydryl Compounds
  • Glucosides
  • Interleukin-18
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • dapagliflozin
  • Fructose
  • Transaminases