PUBLICATION
Protective effect of alpha-lipoic acid and epalrestat on oxaliplatin-induced peripheral neuropathy in zebrafish
- Authors
- Lee, D.W., Park, H.C., Kim, D.H.
- ID
- ZDB-PUB-240201-2
- Date
- 2024
- Source
- Muscle & nerve 69(4): 498-503 (Journal)
- Registered Authors
- Park, Hae-Chul
- Keywords
- alpha-lipoic acid, axonal degeneration, epalrestat, oxaliplatin-induced peripheral neuropathy, zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/toxicity
- Humans
- Oxaliplatin/toxicity
- Peripheral Nervous System Diseases*/chemically induced
- Peripheral Nervous System Diseases*/drug therapy
- Peripheral Nervous System Diseases*/prevention & control
- Rhodanine/analogs & derivatives*
- Thiazolidines*
- Thioctic Acid*/pharmacology
- Thioctic Acid*/therapeutic use
- Zebrafish
- PubMed
- 38294129 Full text @ Muscle Nerve
Citation
Lee, D.W., Park, H.C., Kim, D.H. (2024) Protective effect of alpha-lipoic acid and epalrestat on oxaliplatin-induced peripheral neuropathy in zebrafish. Muscle & nerve. 69(4):498-503.
Abstract
Introduction/aims Oxaliplatin is a platinum-based anti-cancer drug widely used in colorectal cancer patients, but it may cause peripheral neuropathy. As one of the main causes of oxaliplatin-induced peripheral neuropathy (OPN) is oxidative stress, which is also a key factor causing diabetic peripheral neuropathy (DPN), the aim of this study was to evaluate the preventive effects of alpha-lipoic acid (ALA) and epalrestat (EP), which are used for the treatment of DPN, in an OPN zebrafish model.
Methods Tg(nbt:dsred) transgenic zebrafish, with sensory nerves in the peripheral lateral line, were treated with oxaliplatin, oxaliplatin/EP, and oxaliplatin/ALA for 4 days. A confocal microscope was used to visualize and quantify the number of axon bifurcations in the distal nerve ending. To analyze the formation of synapses on sensory nerve terminals, quantification of membrane-associated guanylate kinase (MAGUK) puncta was performed using immunohistochemistry.
Results The number of axon bifurcations and intensity of MAGUK puncta were significantly reduced in the oxaliplatin-treated group compared with those in the embryo medium-treated group. In both the oxaliplatin/EP and oxaliplatin/ALA-treated groups, the number of axon bifurcations and intensity of MAGUK puncta were greater than those in the oxaliplatin-treated group (p < .0001), and no significant difference was observed between larvae treated with oxaliplatin/ALA 1 μM and oxaliplatin/EP 1 μM (p = .4292).
Discussion ALA and EP have protective effects against OPN in zebrafish. Our findings show that ALA and EP can facilitate more beneficial treatment for OPN.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping