Anticancer agents are potent neurotoxins in vitro and in vivo

Annals of Neurology
Wojciech RzeskiChrysanthy Ikonomidou

Abstract

Neurotoxicity of anticancer agents complicates treatment of children with cancer. We investigated neurotoxic effects of common cytotoxic drugs in neuronal cultures and in the developing rat brain. When neurons were exposed to cisplatin (5-100 microM), cyclophosphamide (5-100 microM), methotrexate (5-100 microM), vinblastin (0.1-1 microM), or thiotepa (5-100 microM), a concentration-dependent neurotoxic effect was observed. Neurotoxicity was potentiated by nontoxic glutamate concentrations. The N-methyl-D-aspartate receptor antagonist MK 801 (10 microM), the AMPA receptor antagonists GYKI 52466 (10 microM) and NBQX (10 microM), and the pancaspase inhibitor Ac-DEVD-CHO (1 nM) ameliorated neurotoxicity of cytotoxic drugs. To investigate neurotoxicity in vivo, we administered to 7-day-old rats the following: cisplatin (5-15 mg/kg i.p.), cyclophosphamide (200-600 mg/kg i.p.), thiotepa (15-45 mg/kg), or ifosfamide (100-500 mg/kg) and their brains were analyzed at 4 to 24 hours. Cytotoxic drugs produced widespread lesions within cortex, thalamus, hippocampal dentate gyrus, and caudate nucleus in a dose-dependent fashion. Early histological analysis demonstrated dendritic swelling and relative preservation of axonal terminals, which ar...Continue Reading

References

Dec 1, 1990·Experimental and Molecular Pathology·M G el-BadawiM A Abdalla
May 1, 1988·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·H J GundersenA Vesterby
Apr 16, 1971·Science·J W OlneyA Ratner
Mar 3, 1994·The New England Journal of Medicine·S A Lipton, P A Rosenberg
Feb 1, 1993·Critical Reviews in Oncology/hematology·M HussainM B Edelstein
Jun 1, 1996·Pediatric Research·C IkonomidouJ W Olney
Jan 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G Henze
May 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M L GrahamH S Friedman
Aug 26, 1998·Bone Marrow Transplantation·S SimmsN Bunin
Oct 24, 1998·The Journal of Cell Biology·D S ParkL A Greene
Dec 8, 1998·The Journal of Experimental Medicine·M MüllerP H Krammer
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·D PohlC Ikonomidou
Mar 17, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A N MurphyM F Beal
Mar 1, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S PhippsR K Mulhern
Aug 31, 2000·Neurobiology of Disease·H C Ha, S H Snyder
Dec 2, 2000·Nature·B B Zhou, S J Elledge
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·W RzeskiC Ikonomidou
Jul 13, 2001·Neurobiology of Disease·K DikranianJ W Olney
May 7, 2002·Journal of Pediatric Hematology/oncology·Steven SimmsNancy Bunin
Jan 29, 2003·Current Opinion in Pharmacology·John W Olney
Feb 14, 2003·Current Neurology and Neuroscience Reports·Alyssa T Reddy, Kerry Witek
Jul 25, 2003·British Journal of Haematology·Leslie L Robison, Smita Bhatia
Aug 15, 2003·The New England Journal of Medicine·Ching-Hon PuiMelissa M Hudson
Sep 10, 2003·Biochemical Pharmacology·Abdul-Kader SouidHarvey S Penefsky
Dec 4, 2003·Current Opinion in Cell Biology·Ella Bossy-WetzelStuart A Lipton

❮ Previous
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Citations

Sep 22, 2010·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Kyoung Min LeeJin-hak Lee
Aug 24, 2012·Current Opinion in Oncology·Erin Gibson, Michelle Monje
Dec 9, 2008·The Cancer Journal·Denise D Correa, Tim A Ahles
Nov 23, 2013·PloS One·Marina GenschaftMichael N Smolka
Dec 12, 2012·Breast Cancer : Basic and Clinical Research·Summer F Acevedo
Nov 28, 2013·Neurotoxicity Research·Senthilvelan ManoharRichard Salvi
Aug 21, 2013·Brain Imaging and Behavior·R SeigersJ Dietrich
Mar 22, 2012·Canadian Journal of Physiology and Pharmacology·Mohammad ShabaniNader Shahrokhi
May 31, 2011·Behavioural Brain Research·Michelle Monje, Jörg Dietrich
Apr 5, 2011·Biochemical Pharmacology·Miyoung YangChangjong Moon
Jan 18, 2015·Journal of Theoretical Biology·Kelly C IaroszSergio R Lopes
Aug 26, 2015·Human Brain Mapping·Myrle M Stouten-KempermanSanne B Schagen
Nov 21, 2007·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·R XiaoW Wang
Jul 17, 2013·The International Journal of Neuroscience·Gulfer OzturkErsin Fadillioglu
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Gaylia Jean Harry, Evelyn Tiffany-Castiglioni
Apr 15, 2016·Journal of Adolescent and Young Adult Oncology·Tami D JohnDaniela A Bota
Jul 15, 2015·Brain Imaging and Behavior·D D CorreaN Relkin
Feb 9, 2012·Chemotherapy Research and Practice·G BernocchiF P Fanizzi
Sep 28, 2010·Neuroscience and Biobehavioral Reviews·Riejanne Seigers, Joanna E Fardell
Jun 5, 2014·Psychopharmacology·R SeigersS B Schagen
May 12, 2016·Scientific Reports·Jose Felix Moruno ManchonAndrey S Tsvetkov
Mar 14, 2017·Memory·Oana C LindnerDeborah Talmi
Jun 25, 2015·Acta Cirúrgica Brasileira·Ergun KaraveliogluOlcay Eser
Mar 14, 2007·Bioorganic & Medicinal Chemistry·Wojciech RzeskiMartyna Kandefer-Szerszeń
Aug 9, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianxiu ZhaiWansheng Chen
Oct 30, 2013·Therapeutic Advances in Psychopharmacology·Jayaraman Hariram, Yogaratnam Jegan
Jun 14, 2006·Lasers in Surgery and Medicine·Anna C CroceGiovanni Bottiroli
Jul 29, 2008·Current Opinion in Supportive and Palliative Care·Denise D Correa, Tim A Ahles
Dec 27, 2018·Synapse·Tyler C AlexanderAntiño R Allen

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