Relationship between hepatic mitochondrial functions in vivo and in vitro in rats with carbon tetrachloride-induced liver cirrhosis

Background/Aims: The metabolic capacity of liver mitochondria is impaired i n rats with carbon tetrachloride (CCl4)-induced cirrhosis. These studies me re performed to find out whether benzoate and/or palmitate are suitable sub strates for assessing hepatic mitochondrial function in vivo. Methods: In vivo metabolism of benzoate and 1-C-14-palmitate mas assessed b y monitoring urinary excretion of hippurate and exhalation of (CO2)-C-14, r espectively, in cirrhotic and control rats (n=8 for each group), Isolation of liver mitochondria, and in vitro benzoate and palmitate metabolism mere performed by methods published previously The hepatic content of mitochondr ia was assessed by stereological analysis of the volume of hepatocytes and by biochemical determination, using the activity of citrate synthase. Results: Renal excretion of hippurate following i.p. administration of benz oate was reduced in cirrhotic rats (64+/-15 vs. 85+/-14% of administered do se over 24 h), and showed a linear correlation with hippurate formation by isolated mitochondria, The activities of benzoyl-CoA synthase and benzoyl-C oA:glycine N-acyltransferase mere reduced by approximately 60%, and the coe nzyme A content by 50% in hepatic mitochondria from cirrhotic rats, explain ing impaired hippurate formation, Peak exhalation of (CO2)-C-14 after i.p, administration of 1-C-14-palmitate was reduced by 44% and the area under th e (CO2)-C-14 exhalation-time curve by 34% in cirrhotic rats, Peak (CO2)-C-1 4 exhalation revealed a linear correlation with oxidative metabolism of pal mitoylcarnitine in isolated mitochondria, Both in vivo benzoate and palmita te metabolism showed a linear correlation with the volume fraction of hepat ocytes, The mitochondrial protein content mas reduced in cirrhotic rats per g liver and per liver but equal to control rats per volume of hepatocytes. Conclusions: In vivo metabolism of both palmitate and benzoate reflects hep atic mitochondrial function in rats with CCl4-induced cirrhosis, Hepatic mi tochondrial function is impaired in rats with CCl4-induced cirrhosis due to both reduced mitochondrial volume per liver and impaired metabolism of the remaining mitochondria. In contrast to rats with secondary biliary cirrhos is, rats with CCl4-induced cirrhosis showed no hepatic mitochondrial prolif eration to counteract reduced mitochondrial function.