Oral administration of Cystine and Theanine ameliorates oxaliplatin-induced chronic peripheral neuropathy in rodents

• Published in: Scientific reports 2020-07, Vol.10 (1), p.12665, Article 12665
• Main Authors: Kawashiri, Takehiro, Kobayashi, Daisuke, Egashira, Nobuaki, Tsuchiya, Takashi, Shimazoe, Takao
• Format: Article
• Language: English
• Subjects: 631/378; 631/67; 631/67/1059; 631/67/70; 692/4028; 692/617; Administration, Oral; Animals; Biosynthesis; Cold Temperature; Cystine - administration & dosage; Cystine - pharmacology; Cytotoxicity; Disease Models, Animal; Drug Therapy, Combination; Glutamates - administration & dosage; Glutamates - pharmacology; Glutathione; Glutathione - metabolism; Humanities and Social Sciences; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Male; Mice; multidisciplinary; Neoplasms; Neurodegeneration; Oral administration; Oxaliplatin; Oxaliplatin - adverse effects; Pain perception; PC12 Cells; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - drug therapy; Peripheral Nervous System Diseases - metabolism; Peripheral neuropathy; Rats; Rats, Sprague-Dawley; Sciatic nerve; Sciatic Nerve - metabolism; Science; Science (multidisciplinary); Theanine; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-69674-9

Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. In this study, we investigated the effects of Cystine/Theanine on oxaliplatin-induced peripheral neuropathy using an in vivo model. Repeated injection of oxaliplatin (4 mg/kg intraperitoneally twice a week for 2 weeks) caused mechanical allodynia, cold hyperalgesia and axonal degeneration of the sciatic nerve in rats. Mechanical allodynia and axonal degeneration, but not cold hyperalgesia, were ameliorated by daily co-administration of Cystine [200 mg/kg orally (p.o.)] and Theanine (80 mg/kg p.o.). Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.