Oral administration of Cystine and Theanine ameliorates oxaliplatin-induced chronic peripheral neuropathy in rodents
Oral administration of Cystine and Theanine ameliorates oxaliplatin-induced chronic peripheral neuropathy in rodents
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DOI：
10.1038/s41598-020-69674-9
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发表时间：
2020-07-29
影响因子：
4.6
通讯作者：
Shimazoe, Takao
中科院分区：
文献类型：
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作者：
Kawashiri, Takehiro;Kobayashi, Daisuke;Shimazoe, Takao
奥沙利铂经常导致重度周围神经病变，这是一种剂量限制性毒性。然而，这种毒性缺乏预防策略。胱氨酸/茶氨酸是一种补充剂，其中包括谷胱甘肽生物合成的前体。在这项研究中，我们使用体内模型研究了胱氨酸/茶氨酸对奥沙利铂诱导的周围神经病变的影响。重复腹腔注射奥沙利铂（4 mg/kg，每周两次，持续2周）可引起大鼠坐骨神经的机械性异常性疼痛、冷痛觉过敏和轴突变性。通过每日共同给予胱氨酸[200 mg/kg口服（p.o.）]改善机械性异常性疼痛和轴突变性，但不改善冷痛觉过敏。和茶氨酸（80 mg/kg p.o.）。此外，与奥沙利铂组相比，对大鼠联合给予胱氨酸和茶氨酸显著增加了坐骨神经中的谷胱甘肽水平。此外，胱氨酸和茶氨酸未减弱奥沙利铂在C-26荷瘤小鼠中的肿瘤细胞毒性。这些结果表明，胱氨酸和茶氨酸可能有利于预防奥沙利铂诱导的周围神经病变。
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.