Antioxidants attenuate nuclear factor-kappa B activation and tumor necrosis factor-alpha production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro.
There is increased tumor necrosis factor-alpha (TNF) activity in alcoholic hepatitis (AH).


OBJECTIVE
To examine the effects of antioxidants and glutathione enhancing agents on NF-kappaB activation and TNF production in Kupffer cells and monocytes.


METHODS
Isolated rat Kupffer cells and peripheral blood monocytes from AH patients were treated in vitro. NF-kappaB activation was assessed by electrophoretic mobility shift assay and TNF was measured in cell culture supernatants.


RESULTS
Monocytes from AH patients had greater TNF production compared to normal volunteers. Pretreatment with antioxidants or gluathione enhancing agents inhibited TNF production and NF-kappaB activation in both monocytes from normal and AH patients as well as in rat Kupffer cells.


CONCLUSIONS
There may be a therapeutic role for antioxidants or glutathione enhancing agents in disease states with increased TNF activity such as AH.
Hill
D B
DB
Department of Internal Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Devalaraja
R
R
Joshi-Barve
S
S
Barve
S
S
McClain
C J
CJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000975:Antioxidants; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione