Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy.
For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.
Yang
S
S
Department of Biochemistry, National University of Singapore, MD7, 8 Medical Drive, Singapore 117597, Malaysia.
Tan
T M C
TM
Wee
A
A
Leow
C K
CK
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D006498:Hepatectomy; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011920:Rats, Inbred WF; D013997:Time Factors
D000251:Adenosine Triphosphatases