Cyclosporine A: impact on mitochondrial function in endothelial cells

Clinical Transplantation
Sabine IllsingerAnibh M Das

Abstract

Although cyclosporine A (CSA) is considered to be an efficient immunosuppressive compound in transplantation, vascular side effects like arterial hypertension, neurologic complications and other adverse reactions occur. Interference of CSA with mitochondrial function may be responsible for these side effects. We evaluated the effect of CSA on mitochondrial and glycolytic function by measuring fatty acid oxidation (FAO), activities of respiratory chain complexes (RC) and citratesynthase (CS), lactate/pyruvate-ratios, energy-rich phosphates as well as activities of some glycolytic enzymes in human umbilical vein endothelial cells. After 48 h of CSA incubation, global FAO, RC-complexes 1 + 3; 4 and 5 as well as CS were compromised while energy charges were not reduced. Lactate/pyruvate-ratios increased; cellular lactate dehydrogenase (LDH)-, hexokinase- and phosphofructokinase-activities were not impaired by CSA. Moderate cellular toxicity, assessed by LDH leakage, appeared only at the highest CSA concentration. Part of CSA toxicity may arise from alterations in mitochondrial function as judged by impaired FAO and respiratory chain enzymes. To some extent, energy balance seems to be maintained by cytosolic energy production. Altho...Continue Reading

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Citations

Nov 20, 2013·Journal of Pharmacology & Pharmacotherapeutics·Qu CaihongZhu Jieming
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May 13, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Meike DirksKarin Weissenborn

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