PL EN


Preferences help
enabled [disable] Abstract
Number of results
2007 | 54 | 3 | 583-593
Article title

Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its cyto/genotoxicity in vitro

Content
Title variants
Languages of publication
EN
Abstracts
EN
The function of acetylcholinesterase (AChE) is the rapid hydrolysis of the neurotransmitter acetylcholine (ACh), which is involved in the numerous cholinergic pathways in both the central and the peripheral nervous system. Therefore, AChE measurement is of high value for therapy management, especially during the course of intoxication with different chemicals or drugs that inhibit the enzyme. Pyridinium or bispyridinium aldoximes (oximes) are able to recover the activity of the inhibited enzyme. Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte AChE inhibited by the antineoplastic drug irinotecan as well as its cyto/genotoxicity in vitro were investigated. HI-6 was effective in protection of AChE and increased its activity up to 30%; the residual activity after irinotecan inhibition was 7%. Also, it reactivated the enzyme previously inhibited by 50% irinotecan (4.6 µg/ml) applied at ¼ of the IC50 value. The tested concentrations of HI-6 exhibited acceptable genotoxicity towards white blood cells, as estimated by the alkaline comet assay, DNA diffusion assay and cytogenetic endpoints (structural chromosome aberrations and cytokinesis-block micronucleus assay). The results obtained warrant the further investigation of HI-6 in vivo, as well as its development for possible application in chemotherapy.
Publisher

Year
Volume
54
Issue
3
Pages
583-593
Physical description
Dates
published
2007
received
2007-03-03
revised
2007-06-06
accepted
2007-08-01
(unknown)
2007-08-23
Contributors
  • Institute for Medical Research and Occupational Health, Zagreb, Croatia
  • Institute for Medical Research and Occupational Health, Zagreb, Croatia
  • Institute for Medical Research and Occupational Health, Zagreb, Croatia
author
  • Medical School, University of Zagreb, Zagreb, Croatia
author
  • Institute for Medical Research and Occupational Health, Zagreb, Croatia
  • Institute for Medical Research and Occupational Health, Zagreb, Croatia
References
  • Abigerges D, Armand JP, Chabot GG, Da Costa L, Fadel E, Cote C, Herait P, Gandia D (1994) Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst 86: 446-449.
  • Aguilera L, Martinez-Bourio R, Cid C, Arino JJ, Saez de Eguilaz L, Arizaga A (1988) Anaphylactic reaction after atropine. Anaesthesa 43: 955-957.
  • Bevandic Z, Deljac A, Maksimovic M, Boskovic B, Binenfeld Z (1985) Methylthio analogues of PAM-2, TMB-4 and obidoxime as antidotes in organophosphate poisonings. Acta Pharm Jugosl 35: 213-218.
  • Bugat R, Suc E, Rougier P, Becouarn Y, Naieff I, Ychou M, Culine S, Extra JM, Adenis A, Ganem G (1994) CPT-11 (irinotecan) as second-line therapy in advanced colorectal cancer (CRC): preliminary results of multicentric Phase II study. Proc Annu Meet Am Soc Clin Oncol 13: A586.
  • Clement JG (1982) HI-6: reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat. Biochem Pharmacol 31: 1283-1287.
  • De Jong LPA, Verhagen MAA, Langeberg JP, Hagedorn I, Loffler M (1989) The bispyridinium-dioxime Hlo-7. A potent reactivator for acetylcholinesterase inhibited by stereoisomers of tabun and soman. Biochem Pharmacol 38: 633-640.
  • Dodds HM, Rivory LP (1999) The mechanism for the inhibition of acetylcholinesterases by irinotecan (CPT-11). Mol Pharmacol 56: 1346-1353.
  • Economacos G, Kanakis J (1981) A case of hypersensitivity to atropine. Anesth Analg (Paris) 38: 748.
  • Ellman GL, Courtney KD, Andres VJ, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88-95.
  • Faust F, Kassie F, Knasmuller S, Boedecker RH, Mann M, Mersch-Sundermann V (2004) The use of the alkaline comet assay with lymphocytes in human biomonitoring studies. Mutat Res 566: 209-229.
  • Fenech M, Morley AA (1985) Measurement of micronuclei in lymphocytes. Mutat Res 147: 29-36.
  • Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E (2003) HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534: 65-75.
  • Furman WL, Crews K, Daw NC, Rodriguez-Galindo C, Stewart C, Houghton PJ, Santana VM (2003) Cefixime (CFX) enables further dose-escalation of oral irinotecan (IRN) in pediatric patients with refractory solid tumors. Proc Annu Meet Am Soc Clin Oncol 22: 799.
  • Galosi A, Deljac A, Deljac V, Binenfeld Z (1988) Reactivators of acetylcholinesterase inhibited by organophosphorus compounds. Imidazole derivatives. Acta Pharm Jugosl 38: 23-29.
  • Gandia D, Abigerges D, Armand JP, Chabot G, da Costa L, De Forni M, Mathieu-Boue A, Herait P (1993) CPT-11-induced cholinergic effects in cancer patients (letter). J Clin Oncol 11: 196-197.
  • Goetz MP, Erlichman C, Windebank AJ, Reid JM, Sloan JA, Artherton P, Adjei AA, Rubin J, Pitot H, Galanis E, Ames MM, Goldberg RM (2003) Phase I and Pharmacokinetic Study of two different schedules of oxaliplatin, irinotecan, fluorouracil, and leucovorin in patients with solid tumors. J Clin Oncol 21: 3761-3769.
  • Grisaru D, Sternfeld M, Eldor A, Glick A, Soreq H (1999) Structural roles of acetylcholinesterases variants in biology and pathplogy. Eur J Biochem 264: 672-686.
  • Hecht JR (1998) Gastrointestinal toxicity of irinotecan. Oncology 12: 72-78.
  • Hyatt JL, Tsurkan L, Morton CL, Yoon KJP, Harel M, Brumshtein B, Silman I, Sussman JL, Wadkins RM, Potter PM (2005) Inhibition of acetylcholinesterase by the anticancer prodrug CPT-11. Chem Biol Interact 157/158: 247-252.
  • IAEA (2001) Cytogenetic Analysis for Radiation Dose Assessment. A manual. International Atomic Agency Technical Report Series 405, pp 27-37. IAEA, Vienna,
  • Jonson MK, Jacobsen D, Meredith TJ, Eyer P, Heath AJ, Ligtenstein DA, Marrs TC, Szinicz L, Vale JA, Haines JA (2000) Evaluation of antidotes for poisoning by organophosphorus pesticides. Emerg Med 12: 22-37.
  • Kassa J, Cabal J, Bajgar J, Szinicz L (1997) The choice: HI-6, pralidoxime or obidoxime against nerve agent? ASA Newslett 97: 16-18.
  • Kopjar N, Zeljezic D, Lucic Vrdoljak A, Radic B, Ramic S, Milic M, Gamulin M, Pavlica V, Fucic A (2007) Irinotecan toxicity to human blood cells in vitro - relationships between various biomarkers. Basic Clin Pharmacol Toxicol 100: 403-413.
  • Massoulie J, Anselmet A, Bon S, Krejci E, Legaly C, Morel N, Simon S (1999) The polymorphism of acetylcholinesterase: post-translation processing, quaternary associations and localization. Chem Biol Interact 119/120: 29-42.
  • Mesic M, Deljac A, Deljac V, Binenfeld Z (1991) Reactivators of acetylcholinesterase inhibited by organophosphorus compounds. Imidazole derivatives II. Acta Pharm 41: 203-210.
  • Moller P, Knudsen LE, Loft S, Wallin H (2000) The comet assay as rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors. Cancer Epidemiol Biomarkers Prev 9: 1005-1015.
  • Mortensen SR, Brimijoin S, Hoper MJ, Padilla S (1998) Comparison of the in vitro sensitivity of rat acetylcholinesterase to chlorpyrifos-oxon: what do tissue IC50 values represent? Toxicol Appl Pharmacol 148: 46-49.
  • Morton CL, Wadkins RM, Danks MK, Potter PM (1999) The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalysed to SN-38 by butyrylcholinesterase. Cancer Res 59: 1458-1463.
  • O'Conor PS, Mumma JV (1985) Atropine toxicity. Am J Ophthalmol 99: 613-614.
  • Petit RG, Rothenberg ML, Mitchell EP, Compton LD, Miller LL (1997) Cholinergic symptoms following CPT-11 infusion in a phase II multicenter trial of 250 mg/m2 irinotecan (CRT-11) given every two weeks. Proc Annu Meet Am Soc Clin Oncol 16: A953.
  • Rothenberg ML, Kuhn JG, Burris H, Nelson J, Eckardt JR, Tristan-Morales M, Hilsenbeck SG, Weiss GR, Smith LS, Rodriguez GL (1993) Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol 11: 2194-2204.
  • Sheridan RD, Beeson D, Tattersall JEH (2000) Non-competitive block of the human muscle adult nicotinic acetylcholine receptor ion channel by the bispyridinium compounds, SAD-128 (SAD), toxogonin (TOX) and HI-6. Eur J Neurosci 12 (Suppl S): 36.
  • Singh NP (2000) Microgels for estimation of DNA strand breaks, DNA protein crosslinks and apoptosis. Mutat Res 455: 111-127.
  • Singh NP (2003) Apoptosis by DNA diffusion assay. In: Methods in Molecular Medicine - Chemosensitivity (Blumenthal R, ed) pp 78-94. Humana Press, New York.
  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184-191.
  • Somani SM, Romano JA Jr (2001) Chemical Warfare Agents: Toxicity at low Levels. CRS Press LLC, Boca Raton, Florida.
  • Surralles J, Xamena N, Creus A, Catalan J, Norppa H, Marcos R (1995) Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures. Mutat Res 341: 169-184.
  • Tattersall JEH (1993) Ion channel blockade by oximes and recovery of diaphragm muscle from soman poisoning in vitro. Br J Pharmacol 108: 1006-1015.
  • Taylor P, Radic Z (1994) The cholinesterases: from genes to proteins. Annu Rev Pharmacol Toxicol 34: 281-320.
  • Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35: 206-221.
  • Tobin P, Rivory L, Clarke S (2004) Inhibition of acetylcholinesterase in patients receiving irinotecan (Camptothecin-11). Clin Pharmacol Ther 76: 503-510.
  • US patent 5916903 (1999) Method for reducing the effects of antineoplastic disease treatment.
  • Waadkins RM, Hyatt JL, Yoon KJ, Morton CL, Lee RE, Damodaran K, Beroza P, Danks MK, Potter PM (2004) Discovery of novel selective inhibitors of human intestinal carboxylesterase for the amelioration of irinotecan-induced diarrhea: synthesis, quantitative structure-activity relationship analysis, and biological activity. Mol Pharmacol 65: 1336-1343.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv54p583kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.