Oxidative stress effect on the activation of hepatic stellate cells

Collagen is the most excessive extracellular matrix protein in hepatic fibr osis. Activated, but not quiescent, hepatic stellate cells (HSCs) have a hi gh level of collagen and alpha smooth muscle actin (alpha SMA) expression. HSCs play a key role in the pathogenesis of hepatic fibrosis. We analyzed a mechanism leading to HSC activation by evaluating the role of oxidative st ress and the expression of NFkB. In vitro Study HSCs were proliferated (PCN A:2% vs 68%) and activated( alpha SMA: 5% vs 78%) by ascorbate/FeSO4, and H SCs activated by type I collagen were blocked (PCNA: 97% vs 4%, alpha SMA: 86% vs 9%) by alpha -tocopherol. In vivo study means of alpha SMA positive cells in liver at 400 X HPF were 48.3 +/- 5.2 and 15.2 +/- 1.8 and [H-3]thy midine uptake of HSC was 529.2 +/- 284.8 cpm and 223.0 +/- 86.3 cpm in cont rol and alpha -tocopherol treated group respectively at 32 hours after CCl4 injection. Nuclear extracts from activated, but not from quiescent, HSCs f ormed a complex with the NFkB cognate oligonucleotides and alpha -tocophero l inhibited this bindings. This study indicates that oxidative stress plays an essential role through the induction of NFkB on HSC activation.