REDUCED ANTIOXIDATIVE CAPACITY IN LIVER-MITOCHONDRIA FROM BILE-DUCT LIGATED RATS

Lipid peroxidation and antioxidative mechanisms were investigated in L iver mitochondria from bile duct ligated rats (BDL rats) and correlate d with the activity of enzyme complexes of the electron transport chai n. In comparison to pair-fed control rats, BDL rats had increased conc entrations of thiobarbituric acid reacting substances (TEARS) per gram of liver and per milligram of mitochondrial protein 3, 7, 14, and 28 days after surgery. The hepatic glutathione (GSH) content was decrease d in EDL rats 28 days after surgery when expressed per gram of Liver b ut equal between EDL and control rats when expressed per liver. The mi tochondrial GSH content was decreased in BDL rats by 20% to 33% from d ay 7 after surgery, The concentrations of ubiquinone-9 and ubiquinone- 10, substances involved in electron transport and efficient antioxidan ts, were both decreased in BDL rats 14 and 28 days after surgery per g ram of liver and per milligram of mitochondrial protein. When expresse d per liver, ubiquinone-9 was decreased in BDL rats from day 7 after s urgery. In comparison with controls, the decrease in total mitochondri al ubiquinone content in BDL rats averaged 52% 14 days and 38% 28 days after surgery, The activity of the succinate:ferricytochrome c oxidor eductase (complexes II and III of the electron transport chain) was de creased in EDL rats at days 7, 14, and 28 after surgery, and the activ ity of the ferrocytochrome c:oxygen oxidoreductase (complex IV) was re duced at 14 and 28 days after surgery. The mitochondrial concentration of TEARS showed a negative and the concentrations of GSH and ubiquino ne a positive correlation with the activity of the succinate:ferricyto chrome c oxidoreductase, We conclude that the mitochondrial concentrat ion of antioxidants such as GSH and ubiquinone decreases in BDL rats, whereas the concentration of Lipid peroxidation products increases. He patic mitochondrial dysfunction in BDL rats may at least partially res ult from oxidative damage to mitochondrial lipids and/or proteins.