Early metabolic changes in peripheral blood cells of renal transplant recipients treated with Cyclosporine A

We histochemically examined (phosphatase acid-AcP, phosphatase alkaline-ALP , succinate dehydrogenase-SDH, lactate dehydrogenase-LDH) the peripheral bl ood of renal transplant recipients and controls before (day 0) and after Cy closporine A (CsA) treatment (days 1, 2, 7 and 30). We wanted to detect the metabolic changes induced in the CsA resistant cells (leucocytes) by CsA a nd to evaluate the early effects determined by the drug. There was no diffe rence in enzyme activities between the control group and renal patients bef ore CsA treatment (day 0). AcP and ALP activity increased 1 day after CsA a dministration and became similar to the control by the day 30. LDH activity increased one day after CsA treatment and remained high during the treatme nt period (30 days), while SDH activity did not change. These enzymatic var iations may suggest that the LDH enzyme is involved in the drug degradation as are other phosphatase and oxidoreductase enzymes (i.e. cytochrome P450) . Moreover, the high activity of LDH, the enzyme responsible for interconve rsion of pyruvate in lactic acid, would indicate that anaerobic glycolysis is preferentially used in the pyruvate pathway. However, SDH did not seem t o be directly involved in CsA metabolism. Our findings showed that the CsA treatment induced clear variations of the activity of the cellular phosphat ase and oxidoreductase enzymes from the first days of drug administration. The variation of the enzymes studied and the appearance time and duration o f the metabolic changes, may be markers of the cellular stress due to CsA i nternalization. (C) 1999 International Society for Immunopharmacology. Publ ished by Elsevier Science Ltd. All rights reserved.