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

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-α), 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-α 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-α and TIMP-1.