Human serum butyrylcholinesterase interactions with cisplatin and cyclophosphamide

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Bodur E.

BIOCHIMIE, vol.92, no.8, pp.979-984, 2010 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 92 Issue: 8
  • Publication Date: 2010
  • Doi Number: 10.1016/j.biochi.2010.04.010
  • Journal Name: BIOCHIMIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.979-984
  • Keywords: Butyrylcholinesterase, Cisplatin, Cyclophosphamide, Inhibition, Kinetics, ERYTHROCYTE ACETYLCHOLINESTERASE INHIBITION, CIS-DIAMMINEDIAQUAPLATINUM II, PLASMA CHOLINESTERASE, CAMEL RETINA, KINETICS, CANCER, RISK, COMPLEXES, ALBUMIN, BINDING
  • Hacettepe University Affiliated: Yes

Abstract

Human serum Butyrylcholinesterase (BChE) is an important enzyme in detoxification with its capacity for hydrolyzing esters. The inhibitory effect of cisplatin (CDDP) and cyclophosphamide (CY) on BChE is characterized. Time dependent inhibition of BChE with both chemotherapeutics was rapid, reversible. CY was found as non-competitive inhibitor with Ki of 503.6 +/- 50.4 AM. Time dependent COOP studies displayed progressive inhibition. The constants for apparent dissociation (Ka), first order constant for the break down of the Michaelis complex (k + 2), and bimolecular rate (ka) were calculated as 6.38 x 10(-5) M(-1) min(-1), 0.063 min(-1), and 9.83 x 10(-4) M, respectively. Enzyme protection could be achieved with moderate butyrylthiocholine concentrations (0.3 mM) but higher concentrations increased CDDP inhibition. Apparent Ki value for COOP was 191.8 +/- 71.2 AM. These results suggest that used in combination therapy, CY and CDDP cause considerable BChE inhibition and may aggravate conditions observed during chemotherapy. (C) 2010 Elsevier Masson SAS. All rights reserved.