There is increasing evidence that the integrity of
antioxidant defenses is of vital importance in
extrahepatic cholestasis, particularly with regard to the functioning of the liver's mitochondria. Although the mechanisms by which
cholestasis causes
oxidant/
antioxidant imbalance in mitochondria are poorly understood, hepatic injury caused by
cholestasis may be due to oxidative stress from the mitochondria. The injury has been observed in experimental models of
cholestasis, especial in a model of biliary
cholestasis established in rats with bile duct
ligation (BDL). In the BDL rat model, the
mitochondrial DNA copy number is changed and apoptosis is activated in the liver. In addition, Peroxisome Proliferator-activated Receptor-Coactivator-1alpha and transcriptional
factor A are impaired. Compared to
sham-operated rats,
glutathione activity is decreased after BDL. Peroxidation of the mitochondrial
phospholipids may cause cell
necrosis and the level of a by-product of this peroxidation,
malondialdehyde, may contribute to cell death after BDL. The disturbance of the
oxidant-
antioxidant balance, especially in mitochondria, may be responsible for cholestatic liver injury in
cholestasis rats. This review describes recent development in the pathogenesis of
cholestasis from the viewpoint of mitochondrial biogenesis and suggests possible directions for future study.