Ellagic acid from whole pomegranate fruit reduces liver injury in a rat model of hepatic cholestasis

Open Vet J. 2023 Apr;13(4):466-472. doi: 10.5455/OVJ.2023.v13.i4.8. Epub 2023 Apr 17.

Abstract

Background: Cholestasis is a health problem, both in humans and animals, which in the disease's course involves oxidative stress, inflammation, and liver fibrosis. EA has been proven to have beneficial effects on various diseases.

Aim: This study was conducted to determine the effect of EA in protecting liver damage because of cholestasis. In addition, to understand the underlying mechanism of liver damage in rats as a model animal by bile duct ligation (BDL) technique.

Methods: In this study, male adult rats were used and randomly divided into three treatment groups. S is the sham-operated group, BDL is the group that is treated with BDL and the BDL-EA group is treated with BDL and given EA by gavage at a dose of 60 mg/kg bw/day, starting on the second day after BDL and given for 21 days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) were evaluated using spectrophotometer; tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β1) were evaluated using sandwich ELISA and histopathological examination using HE and Massion's Trichrome staining.

Results: In this study, BDL significantly increased serum levels of AST, ALT, ALP, and hepatic GGT. In addition, BDL also increased levels of TNF-α, and TGF-β1 compared to sham-operated controls. Histological studies in the BDL group also showed that the BDL increased the degree of necro-inflammation and collagen deposition area in the liver compared to the sham-operated group. Administration of EA has been shown to significantly improve liver morpho-function of the liver. I attenuated these changes in the BDL-EA group, where all observed study variables appeared to have improved.

Conclusion: EA has been shown to reduce cholestasis that causes liver injury and improves liver enzyme profiles, and is suspected to have occurred because of its activities as an antioxidant, anti-inflammatory, and anti-fibrotic.

Keywords: BDL; Cholestasis; Ellagic acid; Liver fibrosis.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Animals
  • Cholestasis* / complications
  • Cholestasis* / drug therapy
  • Cholestasis* / metabolism
  • Cholestasis* / veterinary
  • Ellagic Acid / pharmacology
  • Ellagic Acid / therapeutic use
  • Fruit / metabolism
  • Inflammation / veterinary
  • Liver Diseases* / drug therapy
  • Liver Diseases* / etiology
  • Liver Diseases* / prevention & control
  • Liver Diseases* / veterinary
  • Male
  • Pomegranate*
  • Rats
  • Transforming Growth Factor beta1 / therapeutic use
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Ellagic Acid
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha