The role of mitochondria in cholestatic liver injury.
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.
Tiao
Mao-Meng
MM
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Lin
Tsu-Kung
TK
Wang
Pei-Wen
PW
Chen
Jin-Bor
JB
Liou
Cha-Wei
CW
D000818:Animals; D017209:Apoptosis; D002779:Cholestasis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008930:Mitochondria, Liver / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats