Antifibrotic effect of diethylcarbamazine combined with hesperidin against ethanol induced liver fibrosis in rats

Alaa El Din El Sayed El-Sisi, Samia Salim Sokar, Abdelhadi Mohamed Shebl, Dina Zakaria Mohamed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50 mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200 mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100 mg/kg). Liver fibrosis was induced in rats using ethanol (EtOH) (1 ml/100 g/day, p.o.) twice a week for seven weeks. Then, tissue and blood samples were collected to assess the protective effect of DEC + HDN combination. Our results indicated that DEC when combined with HDN blunted EtOH-induced necroinflammation and elevation of liver injury parameters in serum. Besides, attenuated EtOH- induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both DEC and HDN were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) inhibiting the activation of NF-κB as indicated by preventing release of hepatic IL6; (3) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing a-smooth muscle actin (a-SMA) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting serum transforming growth factor-b1 (TGF-b1). Our study indicates a novel hepatoprotective effect when DEC was co-administered with HDN against liver fibrosis.

Original languageEnglish
Pages (from-to)1196-1206
Number of pages11
JournalBiomedicine and Pharmacotherapy
Volume89
DOIs
Publication statusPublished - May 1 2017
Externally publishedYes

Keywords

  • Alcohol
  • IL-6
  • Liver enzymes
  • Oxidative stress
  • Silymarin
  • TGF-β1

ASJC Scopus subject areas

  • Pharmacology

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