Ergothioneine ameliorates oxaliplatin-induced peripheral neuropathy in rats

Autor: Kazuya Takeuchi, Kentaro Nishida, Ayami Hosoda, Eri Morisaki, Shohei Sugano, Kazuki Nagasawa, Akihiro Ohishi
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Organic Cation Transport Proteins
Organoplatinum Compounds
Immunocytochemistry
Antineoplastic Agents
Pharmacology
General Biochemistry
Genetics and Molecular Biology
Antioxidants
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Dorsal root ganglion
Ganglia
Spinal
Medicine
Animals
Carnitine
General Pharmacology
Toxicology and Pharmaceutics
Neurons
Solute Carrier Proteins
Organic cation transport proteins
biology
Symporters
business.industry
Ergothioneine
Membrane Proteins
Peripheral Nervous System Diseases
General Medicine
medicine.disease
Immunohistochemistry
Rats
Oxaliplatin
030104 developmental biology
Peripheral neuropathy
Nociception
medicine.anatomical_structure
nervous system
chemistry
Hyperalgesia
biology.protein
Schwann Cells
medicine.symptom
business
Carrier Proteins
030217 neurology & neurosurgery
medicine.drug
Zdroj: Life sciences. 207
ISSN: 1879-0631
Popis: Aims Oxaliplatin (l-OHP) is a key drug in therapeutic regimens for metastatic or advanced-stage colorectal cancer, but causes peripheral neuropathy as a dose-limiting adverse effect. It is reported that this peripheral neuropathy results from l-OHP accumulation in dorsal root ganglion (DRG) neurons, and that one of the transporters responsible for the accumulation in DRG neurons is organic cation transporter novel (OCTN) 1. Here, we examined whether co-administration of ergothioneine, a substrate/inhibitor of OCTN1, with l-OHP could prevent this peripheral neuropathy. Main methods l-OHP (4 mg/kg, i.p., twice/week, for 6 weeks) and ergothioneine or l -carnitine (1.5 or 15 mg/kg, i.v., twice per l-OHP administration) were administered to rats, and tissue/cellular platinum concentrations and peripheral neuropathy were determined. Expression of transporters in DRG neuronal cells was evaluated by real-time PCR and immunocytochemistry. Key findings On administration of l-OHP to rats, it accumulated in DRG neurons and their mitochondria, while negligible accumulation was found in Schwann cells. Expression of OCTN1 was observed in DRG neurons, especially in small- and medium-sized ones, which are responsible for the nociceptive response. In rats repeatedly administered l-OHP, co-administration of ergothioneine (15 mg/kg), but not l -carnitine, a substrate/inhibitor of OCTN2, decreased l-OHP accumulation in DRGs and development of the mechanical allodynia. Significance These results indicated that l-OHP-induced peripheral neuropathy was ameliorated by co-administration of ergothioneine, at least in part, via a decrease in its accumulation in DRG neurons. Plant diets contain ergothioneine, and thus their consumption might offer relief to patients suffering from l-OHP-induced peripheral neuropathy.
Databáze: OpenAIRE
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