Antifibrotic effects of bezafibrate and pioglitazone against thioacetamide-induced liver fibrosis in albino rats

Salwa A. Ibrahim*, Mervat Z. Mohamed, Nashwa F. El-Tahawy, Aly M. Abdelrahman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of hepatic stellate cells is a central event in hepatic fibrogenesis that offers multiple potential sites for therapeutic interventions. Peroxisome proliferator-activated receptors are implicated in liver fibrosis. We aimed to evaluate the effect of bezafibrate and pioglitazone on a thioacetamide (TAA) rat model of liver fibrosis and to clarify the possible underlying mechanisms. Rats received intraperitoneal injections of TAA for 6 weeks. Daily oral treatments with bezafibrate or pioglitazone were started with the first day of TAA intoxication. Serum liver function tests, hepatic malondialdehyde (MDA), total nitrite and nitrate (NOx), superoxide dismutase, and hepatic histopathology were assessed to evaluate hepatic damage. Alpha smooth muscle actin (α-SMA) and tissue inhibitor metalloproteinase-1 (TIMP-1) and caspase-3 were also assessed. The TAA group experienced significant deterioration of liver functions, increased oxidative stress, and increased liver tissue NOx. Administration of bezafibrate or pioglitazone resulted in significant improvement of all liver functions and reduced oxidative stress in hepatic tissues. Only administration of bezafibrate significantly reduced NOx levels. Liver tissues from the TAA-treated group showed disrupted normal architecture. Administration of bezafibrate or pioglitazone attenuated this picture. Stronger α-SMA expression was detected in the TAA group. Treatment with bezafibrate or pioglitazone decreased the α-SMA expression.

Original languageEnglish
Pages (from-to)313-320
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume99
Issue number3
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

  • Antifibrotic
  • Antioxidants
  • Bezafibrate
  • Liver fibrosis
  • Pioglitazone
  • PPAR
  • Thioacetamide

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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