Document Detail

Modulation of Fas-FasL related apoptosis by PBN in the early phases of choline deficient diet-mediated hepatocarcinogenesis in rats.
MedLine Citation:
PMID:  17729114     Owner:  NLM     Status:  MEDLINE    
This study focused on the detection of apoptosis related events in very early phases of choline-deficient (CD)-induced hepatocarcinogenesis (at 2-5 weeks). Flow cytometry of isolated intact primary hepatocytes from CD diet fed rats indicated increased expression of the apoptosis-associated protein Fas. Increased apoptosis in CD-treated livers was confirmed by Western blot analyses of caspases and cytochrome c. This study was also able to detect differences in apoptotic events following phenyl butyl nitrone (PBN) treatment. Fas expression was inhibited by PBN, indicating that PBN is anti-apoptotic. It is speculated that in the early stages of CD-induced hepatotoxicity, PBN is involved in inhibiting pro-inflammatory factor-driven apoptosis of normal hepatocytes, which protects against the initiation of carcinogenesis. The CD diet model is also considered as a model for non-alcoholic steatohepatitis (NASH) in humans and early expression of Fas could also be a good index of the progression of NASH.
Yoshiko Inoue; Taketoshi Asanuma; Nataliya Smith; Debra Saunders; Jenny Oblander; Yashige Kotake; Robert A Floyd; Rheal A Towner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Free radical research     Volume:  41     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-30     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  972-80     Citation Subset:  IM    
Free Radical Biology and Aging Research Program, Oklahoma City, OK 73104, USA.
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MeSH Terms
Antigens, CD95 / antagonists & inhibitors*,  metabolism
Apoptosis / drug effects
Cell Transformation, Neoplastic / metabolism*,  pathology
Choline / administration & dosage
Choline Deficiency / complications*
Cyclic N-Oxides / pharmacology*
Free Radical Scavengers / pharmacology*
Liver / drug effects,  pathology
Liver Neoplasms / etiology*,  metabolism,  pathology
Grant Support
Reg. No./Substance:
0/Antigens, CD95; 0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Tnfrsf6 protein, rat; 3376-24-7/phenyl-N-tert-butylnitrone; 62-49-7/Choline

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