Combination of Sitagliptin and Silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats

Samia Salem Sokar, Magda El Sayed El-Sayad, Mai El Sayed Ghoneim*, Abdelhadi Mohamed Shebl

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl4) rat model. Male albino rats received intraperitoneal injections of CCl4 three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100 mg/kg) or Silymarin (100 mg/kg) or their combination during the 7 weeks of intoxication. Hepatic fibrotic changes were evaluated by measuring hepatic enzymes (ALT, AST, ALP, and GGT) and markers of fibrosis (transforming growth factor β1 (TGF-β1), tissue 4-hydroxyproline level, histopathological score), oxidative stress (MDA, GSH, and NOx levels), inflammation (interleukin-6) as well as markers of HSCs activation (α-smooth muscle actin (α-SMA) expression). The injected rats with CCl4 for 7 weeks resulted in a marked elevation of hepatic fibrotic changes and reduction of GSH level, while the combination therapy showed a significant decrease in the former one and a significant increase in the later. In conclusion, this study shows that the combination therapy is more beneficial than monotherapy in ameliorating liver fibrosis in rats. Our findings suggest that Sitagliptin alone or in combination with Silymarin may introduce a new strategy for treating liver fibrosis in humans.

Original languageEnglish
Pages (from-to)98-107
Number of pages10
JournalBiomedicine and Pharmacotherapy
Publication statusPublished - May 1 2017
Externally publishedYes


  • Carbon tetrachloride
  • Liver fibrosis
  • Silymarin
  • Sitagliptin

ASJC Scopus subject areas

  • Pharmacology

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