Protective effects of paclitaxel on thioacetamide-induced liver fibrosis in a rat model.

Abstract

Liver fibrosis is a public health burden that is highly associated with morbidity and mortality. Therefore, this study aims to explore the anti-fibrotic effects of low dose of paclitaxel (PTX) against thioacetamide (TAA)-induced liver fibrosis in rats and the possible mechanisms involved. TAA was administered at a dose of 200 mg/kg twice weekly for 6 weeks in rats to induce liver fibrosis similar to that in humans. Liver dysfunction was shown by increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase, along with histopathological changes. Liver fibrosis was confirmed by Masson's Trichome staining, increased collagen content, and elevated α-smooth muscle actin (α-SMA) protein expression. In addition, TAA induced liver apoptosis as indicated by the increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in liver tissues. This study demonstrated that the administration of PTX (0.3 mg/kg/i.p.) three times a week for 6 weeks significantly alleviated functional and biochemical changes induced by TAA in addition to improving the liver architecture. PTX attenuated liver fibrosis as reflected by the decreased collagen content and α-SMA protein expression. Additionally, PTX attenuated liver apoptosis as indicated by the decreased TUNEL-positive cells. Moreover, PTX prevented TAA-induced elevation of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels in liver tissues. These findings suggest that the low dose of PTX prevented TAA-induced liver fibrosis in rats, possibly by inhibiting the expression of TGF-β1 and PDGF-BB and subsequently suppressing the apoptosis and the expression of TIMP-1.

• Authors: Maha H Sharawy, Mohammed S El-Awady, Mirhan N Makled
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 35 Issue 5 Pg. e22745 (May 2021) ISSN: 1099-0461 [Electronic] United States
• PMID: 33749060 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Thioacetamide
• Paclitaxel

Topics

• Animals
• Disease Models, Animal
• Liver Cirrhosis (chemically induced, metabolism, prevention & control)
• Male
• Paclitaxel (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Thioacetamide (toxicity)