Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy
| Autor: | Helmar C. Lehmann, Abhijeet R. Joshi, Ilja Bobylev, Helina Maru |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Male Sensory Receptor Cells Schwann cell Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Medicine Animals heterocyclic compounds Pharmacology (medical) Cells Cultured Skin business.industry Linezolid Peripheral Nervous System Diseases biochemical phenomena metabolism and nutrition bacterial infections and mycoses medicine.disease Sciatic Nerve Sensory neuron Anti-Bacterial Agents Mitochondria Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases medicine.anatomical_structure Peripheral neuropathy chemistry Peripheral nervous system bacteria Sciatic nerve Schwann Cells business 030217 neurology & neurosurgery |
| Zdroj: | The Journal of antimicrobial chemotherapy. 71(3) |
| ISSN: | 1460-2091 |
| Popis: | OBJECTIVES 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. METHODS 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. RESULTS 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(+)/Ca(2+) exchanger blocker KB-R7943. CONCLUSIONS 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. |
| Databáze: | OpenAIRE |
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