Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver

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Abstract
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 < 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 ATPutilizing reactions in an early process of liver regeneration.