Early perturbations in keratin and actin gene expression and fibrillar organisation in griseofulvin-fed mouse liver

摘要: Abstract Background/Aims: Long-term feeding of mice with a diet containing griseofulvin results in the formation Mallory bodies, keratin K8 and K18 aggregates hepatocytes. These bodies are biochemically morphologically identical to that emerge several human liver disorders. The aim this study was examine contribution actin body formation. Methods: Mice were fed over period ranging from 1 day 20 months. Hepatocyte morphology monitored by immunocytochemistry, gene expression Northern run-off transcription assays, protein level Western blotting. Results: Griseofulvin induced series morphological alterations hepatocytes could be grouped into 3 phases: appearance cholestasis during first week (phase I), partial hepatocyte recovery at months II), development typical after 5 III). All these cellular associated perturbations fibrillar status, coupled increases K8, mRNA steadystate and, content. transcriptional activity genes not affected. Conclusions: Perturbations organisation constitute early events griseofulvin-induced pathological process long-term leads higher levels reflect significant stability taking place phase intoxication