The role of iron in neurotoxicity: A study of novel antimalarial drugs

S. L. Smith; J. L. Maggs; G. Edwards; S. A. Ward; B. K. Park; W. G. McLean

The role of iron in neurotoxicity: A study of novel antimalarial drugs

S. L. Smith, J. L. Maggs, G. Edwards, S. A. Ward, B. K. Park, W. G. McLean

University of Liverpool

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vive and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 μM artemether (AEM) in the presence of 2 μM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 μM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3α- hydroxydesoxyartemether.

Original language	English
Pages (from-to)	557-560
Number of pages	4
Journal	NeuroToxicology
Volume	19
Issue number	4-5
Publication status	Published - 1 Sept 1998
Externally published	Yes

Keywords

Artemisinin
Free Radicals
Iron
Neurite
Neurotoxicity

Cite this

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title = "The role of iron in neurotoxicity: A study of novel antimalarial drugs",

abstract = "The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vive and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 μM artemether (AEM) in the presence of 2 μM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76\%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 μM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3α- hydroxydesoxyartemether.",

keywords = "Artemisinin, Free Radicals, Iron, Neurite, Neurotoxicity",

author = "Smith, \{S. L.\} and Maggs, \{J. L.\} and G. Edwards and Ward, \{S. A.\} and Park, \{B. K.\} and McLean, \{W. G.\}",

year = "1998",

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language = "English",

volume = "19",

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TY - JOUR

T1 - The role of iron in neurotoxicity

T2 - A study of novel antimalarial drugs

AU - Smith, S. L.

AU - Maggs, J. L.

AU - Edwards, G.

AU - Ward, S. A.

AU - Park, B. K.

AU - McLean, W. G.

PY - 1998/9/1

Y1 - 1998/9/1

N2 - The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vive and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 μM artemether (AEM) in the presence of 2 μM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 μM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3α- hydroxydesoxyartemether.

AB - The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vive and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 μM artemether (AEM) in the presence of 2 μM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 μM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3α- hydroxydesoxyartemether.

KW - Artemisinin

KW - Free Radicals

KW - Iron

KW - Neurite

KW - Neurotoxicity

UR - https://www.scopus.com/pages/publications/0031715091

M3 - Article

C2 - 9745911

AN - SCOPUS:0031715091

SN - 0161-813X

VL - 19

SP - 557

EP - 560

JO - NeuroToxicology

JF - NeuroToxicology

IS - 4-5

ER -

The role of iron in neurotoxicity: A study of novel antimalarial drugs

Abstract

Keywords

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