Colacino J M
Infectious Diseases Research, Lilly Research Laboratories, Indianapolis, IN 46285-0438, USA.
Antiviral Res. 1996 Mar;29(2-3):125-39. doi: 10.1016/0166-3542(95)00836-5.
Fialuridine (FIAU) is a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. In a clinical evaluation for its use as a treatment for chronic HBV infection, long term (HBV) in vitro and in vivo. In a clinical evaluation for its term oral administration of FIAU resulted in severe multi-organ toxicity characterized by a delayed onset and refractory lactic acidosis. These clinical manifestations led to the hypothesis that the toxicity of FIAU was mediated through mitochondrial dysfunction, possibly as a result of the inhibition of mitochondrial DNA polymerase gamma and/or incorporation of FIAU into mitochondrial DNA. In addition to describing the anti-HBV activity of FIAU, this review discusses results from in vitro experiments carried out by various laboratories in an effort to evaluate and understand more fully the mitochondrial toxicity of FIAU.
氟苷（FIAU）是一种胸腺嘧啶核苷类似物，在体外和体内对多种疱疹病毒和乙型肝炎病毒（HBV）具有活性。在一项将其用作慢性HBV感染治疗方法的临床评估中，长期口服FIAU会导致严重的多器官毒性，其特征为迟发性发作和难治性乳酸性酸中毒。这些临床表现引发了一种假说，即FIAU的毒性是通过线粒体功能障碍介导的，这可能是由于线粒体DNA聚合酶γ受到抑制和/或FIAU掺入线粒体DNA所致。除了描述FIAU的抗HBV活性外，本综述还讨论了各个实验室进行的体外实验结果，以便更全面地评估和了解FIAU的线粒体毒性。
