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Protective effects of paclitaxel on thioacetamide‐induced liver fibrosis in a rat model
Author(s) -
Sharawy Maha H.,
ElAwady Mohammed S.,
Makled Mirhan N.
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22745
Subject(s) - thioacetamide , tunel assay , fibrosis , endocrinology , terminal deoxynucleotidyl transferase , medicine , liver injury , chemistry , hepatic stellate cell , apoptosis , biochemistry
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.