Early metabolic changes in peripheral blood cells of renal transplant recipients treated with Cyclosporine A R. Rezzani, L. Rodella, R. Bianchi* Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, Via Valsabbina, 19-25123, Brescia, Italy Received 29 December 1998; accepted 5 April 1999 Abstract We histochemically examined (phosphatase acid-AcP, phosphatase alkaline-ALP, succinate dehydrogenase-SDH, lactate dehydrogenase-LDH) the peripheral blood of renal transplant recipients and controls before (day 0) and after Cyclosporine 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 and to evaluate the early eects determined by the drug. There was no dierence in enzyme activities between the control group and renal patients before CsA treatment (day 0). AcP and ALP activity increased 1 day after CsA administration and became similar to the control by the day 30. LDH activity increased one day after CsA treatment and remained high during the treatment period (30 days), while SDH activity did not change. These enzymatic variations 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 interconversion of pyruvate in lactic acid, would indicate that anaerobic glycolysis is preferentially used in the pyruvate pathway. However, SDH did not seem to be directly involved in CsA metabolism. Our ®ndings showed that the CsA treatment induced clear variations of the activity of the cellular phosphatase and oxidoreductase enzymes from the ®rst days of drug administration. The variation of the enzymes studied and the appearance time and duration of the metabolic changes, may be markers of the cellular stress due to CsA internalization. # 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. Keywords: Cyclosporine A; Renal transplant; Histochemistry; Peripheral blood International Journal of Immunopharmacology 21 (1999) 455±462 0192-0561/99/$20.00 # 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved. PII: S0192-0561(99)00026-0 www.elsevier.com/locate/ijimmpharm * Corresponding author Tel.: +39-30-3717303; fax: +39-30-3701157. E-mail address: bianchi@med.unibs.it (R. Bianchi)