eISSN: 2449-8238
ISSN: 2392-1099
Clinical and Experimental Hepatology
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SCImago Journal & Country Rank
3/2018
vol. 4
 
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abstract:
Original paper

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

Mohamed A. Ibrahim, Asmaa Abdel-Aziz, Azza El-Sheikh, Maha Kamel, Al-Zahraa Khalil, Hisham Abdelhaleem

Clin Exp HEPATOL 2018; 4, 3: 175–181
Online publish date: 2018/09/10
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Introduction
The study aimed at investigating the hepatic effect of direct acting anti-hepatitis C virus drugs (DAAs), sofosbuvir (Sof) and daclatasvir (Dac), in thioacetamide (TAA)-induced liver injury in rats.

Material and methods
Animals were allocated to 7 groups: a normal control group, a TAA group (receiving TAA 50 mg/kg, i.p. twice weekly), two TAA groups receiving either a low or a high dose of Sof (Sof-L and Sof-H; 41.1 mg/kg and 82.2 mg/kg, respectively), two TAA groups receiving either a low or a high dose of Dac (Dac-L and Dac-H; 6.2 mg/kg and 12.4 mg/kg, respectively), and a TAA group receiving both Sof-L and Dac-L.

Results
After 6 weeks, TAA significantly elevated the serum activities of liver enzymes, along with histopathological evidence of liver injury. These findings were associated with a significant increase in a fibrotic marker (tissue inhibitor metalloproteinase-1 – TIMP-1), proinflammatory cytokine (tumor necrosis factor alpha – TNF-), and oxidative stress parameters (malondialdehyde [MDA] content, and superoxide dismutase [SOD] and catalase activities) in hepatic tissue. TAA rats treated with Sof-L, Dac-L, Dac-H and a combination of Sof-L plus Dac-L showed significant amelioration of TAA-induced liver injury. Their effects were accompanied by a significant reduction in TIMP-1, TNF- and oxidative stress parameters in hepatic tissue. Interestingly, Sof-H caused no improvement in TAA-induced hepatic injury.

Conclusions
The hepatic effects of Sof and Dac in TAA-induced liver injury appeared to be mediated by anti-oxidant effects, and inhibition of TNF- and TIMP-1.

keywords:

daclatasvir, sofosbuvir, liver injury, thioacetamide

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