Abstract
Paclitaxel causes a sensory polyneuropathy with characteristic features of distal axonal degeneration. Although the exact mechanisms underlying distal axonal degeneration are unknown, paclitaxel-induced axonal degeneration has been shown to be associated with an increase in detyrosinated tubulin. Here we show that recombinant human erythropoietin prevents axonal degeneration in sensory neurons in vitro and this effect is associated with downregulation of detyrosinated tubulin. Furthermore, in an animal model of paclitaxel-induced distal sensory polyneuropathy, recombinant human erythropoietin protects against distal axonal degeneration. These findings suggest that recombinant human erythropoietin may be useful as a therapy to prevent paclitaxel-induced sensory polyneuropathy in patients undergoing chemotherapy.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / adverse effects*
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Axons / drug effects
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Axons / physiology*
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Carriers / adverse effects
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Erythropoietin / administration & dosage
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Erythropoietin / physiology*
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Female
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Ganglia, Spinal / cytology
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Glycerol / adverse effects
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Glycerol / analogs & derivatives
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Humans
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Injections, Intraperitoneal
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Mice
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Nerve Degeneration / chemically induced
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Nerve Degeneration / prevention & control*
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Neurons, Afferent / drug effects
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Neurons, Afferent / physiology*
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Neuroprotective Agents / administration & dosage
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Paclitaxel / adverse effects*
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Recombinant Proteins
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Tubulin / drug effects
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Tubulin / metabolism
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Tyrosine
Substances
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Antineoplastic Agents, Phytogenic
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Drug Carriers
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Neuroprotective Agents
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Recombinant Proteins
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Tubulin
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Erythropoietin
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Tyrosine
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cremophor EL
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Paclitaxel
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Glycerol