A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C
| Autor: | Kip Lyche, Mario Chojkier, K Houglum, Arjun Venkataramani |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Pathology Transcription Genetic Hepatitis C virus Biopsy Inflammation Pilot Projects medicine.disease_cause chemistry.chemical_compound Proto-Oncogene Proteins c-myb Fibrosis Internal medicine Malondialdehyde Proto-Oncogene Proteins Proto-Oncogenes medicine Humans Vitamin E RNA Messenger In Situ Hybridization Hepatology medicine.diagnostic_test business.industry Gastroenterology Middle Aged medicine.disease Hepatic stellate cell activation Hepatitis C Actins Oxidative Stress Endocrinology chemistry Liver Liver biopsy Hepatic stellate cell Trans-Activators Female Collagen medicine.symptom business Oxidative stress |
| Zdroj: | Gastroenterology. 113(4) |
| ISSN: | 0016-5085 |
| Popis: | BACKGROUND & AIMS: Oxidative stress mediates activation and stimulates collagen production of cultured hepatic stellate (Ito) cells. The aim of this study was to assess whether oxidative stress contributes to hepatic fibrogenesis in chronic hepatitis C. METHODS: In liver biopsy specimens of patients with chronic hepatitis C, the following fibrogenesis cascade was analyzed: (1) oxidative stress, determined by the presence of malondialdehyde protein adducts; (2) activation of stellate cells as indicated by their expression of alpha-smooth muscle actin; (3) stimulation of c-myb expression in stellate cells, a critical step in the activation of these cells; and (4) induction of collagen gene expression as detected by in situ hybridization. RESULTS: Treatment with d-alpha-tocopherol (1200 IU/day for 8 weeks) in 6 of these patients, who were refractory to interferon therapy, prevented the fibrogenesis cascade observed before antioxidant treatment. In addition, d-alpha-tocopherol treatment significantly decreased the carbonyl modifications of plasma proteins, a sensitive index of oxidative stress. However, 8 weeks of d-alpha-tocopherol treatment did not significantly affect serum alanine aminotransferase levels, hepatitis C virus titers, or histological degree of hepatocellular inflammation or fibrosis. CONCLUSIONS: These data suggest that enhanced oxidative stress initiates a fibrogenesis cascade in the liver of patients with chronic hepatitis C. (Gastroenterology 1997 Oct;113(4):1069-73) |
| Databáze: | OpenAIRE |
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