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Reduced activity of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis
Author(s) -
Krähenbühl Stefan,
Stucki Jörg,
Reichen Jürg
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150630
Subject(s) - mitochondrion , medicine , endocrinology , bile duct , ligation , cirrhosis , chemistry , cholesterol , phospholipid , biology , biochemistry , membrane
Mitochondrial metabolism was studied in liver mitochondria isolated from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk. State 3 oxidation rates were decreased in mitochondrial preparations from bile duct—ligated rats as compared with sham‐operated control rats by 63% and 42% using β‐hydroxybutyrate and succinate as substrates, respectively. In contrast, when the substrate was ascorbate/ N , N , N ′, N ′‐tetramethyl‐ p ‐phenylenediamine state 3 oxidation rates were not affected by bile duct ligation. Oxidation rates after uncoupling with dinitrophenol were decreased for both β‐hydroxybutyrate and succinate as substrates in mitochondria from bile duct—ligated rats. The phosphate potential was reduced in mitochondria from bile duct—ligated rats (12.5 ± 0.5 vs. 13.6 ± 0.2 kcal in control and bile duct—ligated rats, respectively; p<0.05). The inner mitochondrial membrane of liver mitochondria from rats with secondary biliary cirrhosis contained three times more cholesterol as compared with control rats, whereas the phospholipid composition was essentially unchanged. Mitochondrial protein content expressed per liver (calculated on the basis of activities of mitochondrial enzymes determined in liver homogenate and in isolated mitochondria) was increased by 50% in bile duct—ligated rats as compared with control rats. In conclusion, the function of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis is impaired. This decrease could be related to altered lipid composition of the inner mitochondrial membrane. (H EPATOLOGY 1992;15:1160‐1166).