Abstract
Aims. To measure the expression of activin βA-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-α (Peg-INF-α) and ribavirin (RBV). Materials and Methods. 40 male Wistar rats were divided equally into 4 groups: “control,” “Peg-only” receiving 4 injections of Peg-INF-α (6 µg/rat/week), “RBV-only” receiving ribavirin (4 mg/rat/day) orally, and “Peg & RBV” group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA. Results. Peg-INF-α ± RBV altered the expression of all candidate molecules in the liver at the gene and protein levels (P < 0.05) and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groups (P < 0.05). There were also significant correlations between serum and liver activin-A and follistatin. Conclusion. Peg-INF-α modulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-α on the production of activins and follistatin by the liver and immune cells.
Highlights
Infection with hepatitis C virus (HCV) is a global health problem and it is a leading cause for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma [1]
New directly acting antiviral drugs (DAAs) have been developed for the treatment of chronic hepatitis C (CHC), these drugs are expensive and pegylated interferon-α- (Peg-INF-α-) 2a or 2b plus a daily weight-based dose of ribavirin could still be the standard of care especially for the treatment of naıve patients with compensated liver functions and/or for those living in developing countries and for whom access to the new drugs is not definite [2,3,4,5,6,7]
All molecules were detected in the liver sections of all groups and the immunostain was localised in the cell membrane and cytoplasm of hepatocyte surrounding hepatic vessels (Figures 1–3)
Summary
Infection with hepatitis C virus (HCV) is a global health problem and it is a leading cause for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma [1]. New directly acting antiviral drugs (DAAs) have been developed for the treatment of chronic hepatitis C (CHC), these drugs are expensive and pegylated interferon-α- (Peg-INF-α-) 2a or 2b plus a daily weight-based dose of ribavirin could still be the standard of care especially for the treatment of naıve patients with compensated liver functions and/or for those living in developing countries and for whom access to the new drugs is not definite [2,3,4,5,6,7]. The present study was conducted to measure the effects of Peg-INF-α based therapy on the expression of activin βA-subunit, activin type IIA and IIB receptors, Smad, Smad, and follistatin in liver tissue collected from normal Wistar rat since it is not ethically possible to inject healthy human subjects with unnecessary drugs. The effects of Peg-INF-α based therapy on the concentrations of the mature activin-A and follistatin proteins were measured in liver homogenates and serum samples collected from the animals
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