Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver.
The effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P less than 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATP-utilizing reactions in an early process of liver regeneration.
Uemoto
S
S
Second Department of Surgery, Kyoto University, Faculty of Medicine, Japan.
Tanaka
K
K
Asonuma
K
K
Okamura
R
R
Kitakado
Y
Y
Matsuoka
S
S
Ozaki
N
N
Ozawa
K
K
Hashida
T
T
Inui
K
K
D000227:Adenine Nucleotides / Q000032:analysis; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D006498:Hepatectomy; D007700:Kinetics; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D003524:Cyclosporins; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate