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AIM:To elucidate the effect of antioxidants,resveratrol (RVT) and astaxanthin (AXN),on hepatitis C virus (HCV)replication.METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6.RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses.AXN is also a strong antioxidant.The replication of HCV RNA was assessed by the luciferase reporter assay.An additive effect of antioxidants on antiviral effects of interferon (IFN) and ribavirin (RBV)was investigated.RESULTS:This is the first report to investigate the effect of RVT and AXN on HCV replication.In contrast to other reported viruses,RVT significantly enhanced HCV RNA replication.Vitamin E also enhanced HCV RNA replication as reported previously,although AXN didnot affect replication.IFN and RBV significantly reduced HCV RNA replication,but these effects were dose-dependently hampered and attenuated by the addition of RVT.AXN didnot affect antiviral effects of IFN or RBV.CONCLUSION:These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.