Universität zu Köln

Bobylev, Ilja, Maru, Helina, Joshi, Abhijeet R. and Lehmann, Helmar C. (2016). Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy. J. Antimicrob. Chemother., 71 (3). S. 685 - 692. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na+/Ca2+ exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bobylev, Ilja UNSPECIFIED UNSPECIFIED UNSPECIFIED Maru, Helina UNSPECIFIED UNSPECIFIED UNSPECIFIED Joshi, Abhijeet R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Helmar C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-282654
DOI:	10.1093/jac/dkv386
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	71
Number:	3
Page Range:	S. 685 - 692
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DRUG-RESISTANT TUBERCULOSIS; AXONAL DEGENERATION; IN-VIVO; MULTIDRUG-RESISTANT; OPTIC NEUROPATHY; TOLERABILITY; ENTEROCOCCI; VANCOMYCIN; MECHANISMS; EFFICACY Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28265