Hepatic effect of sofosbuvir and daclatasvir in thioacetamide-induced liver injury in rats

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Mohamed A Ibrahim1, Asmaa Abdel-Aziz1, Azza El-Sheikh1

  • 1Faculty of Medicine, Minia University, Egypt.

Clinical and Experimental Hepatology
|October 17, 2018
PubMed
Abstract

Insights

Direct-acting antivirals sofosbuvir and daclatasvir showed protective effects against thioacetamide-induced liver injury in rats. These drugs reduced liver damage by decreasing inflammation and oxidative stress.

Area of Science:

  • Hepatology
  • Pharmacology
  • Toxicology

Background:

  • Thioacetamide (TAA) is a hepatotoxin used to induce liver injury in animal models.
  • Direct-acting antivirals (DAAs) like sofosbuvir (Sof) and daclatasvir (Dac) are primarily used for Hepatitis C treatment.
  • The hepatic effects of DAAs in non-viral liver injury models are not well-established.

Purpose of the Study:

  • To investigate the protective effects of sofosbuvir (Sof) and daclatasvir (Dac) on thioacetamide (TAA)-induced liver injury in a rat model.
  • To evaluate the impact of DAAs on liver enzymes, fibrotic markers, inflammatory cytokines, and oxidative stress parameters in TAA-induced hepatotoxicity.

Main Methods:

  • Rats were induced with liver injury using thioacetamide (TAA).
  • Animals were treated with varying doses of sofosbuvir (Sof-L, Sof-H) and daclatasvir (Dac-L, Dac-H), or a combination of Sof-L and Dac-L.
  • Hepatic injury was assessed by measuring serum liver enzymes, histopathology, and hepatic levels of TIMP-1, TNF-α, MDA, SOD, and catalase.

Main Results:

  • TAA administration significantly increased liver enzymes, fibrosis (TIMP-1), inflammation (TNF-α), and oxidative stress (MDA, decreased SOD and catalase).
  • Treatment with low-dose sofosbuvir (Sof-L), low-dose daclatasvir (Dac-L), high-dose daclatasvir (Dac-H), and the combination of Sof-L plus Dac-L significantly ameliorated TAA-induced liver injury.
  • These protective effects were associated with significant reductions in TIMP-1, TNF-α, and oxidative stress markers.
  • High-dose sofosbuvir (Sof-H) did not show any significant improvement in TAA-induced hepatic injury.

Conclusions:

  • Sofosbuvir and daclatasvir demonstrate hepatoprotective effects in a rat model of TAA-induced liver injury.
  • The therapeutic mechanisms involve antioxidant properties and the inhibition of TNF-α and TIMP-1.
  • Daclatasvir, particularly at higher doses or in combination with sofosbuvir, appears more effective than sofosbuvir alone in this model.
Keywords:
daclatasvirliver injurysofosbuvirthioacetamide

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