Glutathione alleviated peripheral neuropathy in oxaliplatin-treated mice by removing aluminum from dorsal root ganglia

Minji Lee, Sungrae Cho, Kangsan Roh, Jisook Chae, Jin Hee Park, Jaehyun Park, Myung Ah Lee, Jinheung Kim, Chung Kyoon Auh, Chang Hwan Yeom, Sukchan Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Oxaliplatin, a platinum-based anti-cancer drug, induces peripheral neuropathy as a side effect and causes cold hyperalgesia in cancer patients receiving anti-cancer chemotherapy. In oxaliplatin-treated mice, aluminum was accumulated in the dorsal root ganglia (DRG), and accumulated aluminum in DRG or other organs aggravated oxaliplatin-induced neuropathic pain. To investigate whether aluminum oxalate, which is the compound of aluminum and oxaliplatin, might be the peripheral neuropathy inducer, the withdrawal responses of mice to coldness, the expression of transient receptor potential ankyrin 1 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays in DRG were analyzed in mice administered with aluminum oxalate. In addition, the concentrations of aluminum in aluminum oxalate-treated mice were significantly increased compared to those of mice treated with aluminum chloride. To alleviate neuropathic pain, glutathione (GSH), known as an antioxidant and a metal chelator, was injected into oxaliplatin-treated mice. The concentrations of aluminum in the DRG were decreased by the chelation action of GSH. Taken together, behavioral and molecular analyses also supported that aluminum accumulation on the DRG might be a factor for neuropathic pain. This result also suggested that the aluminum chelation by GSH can provide an alleviatory remedy of neuropathic pain for cancer patients with oxaliplatin-induced neuropathic pain.

Original languageEnglish
Article numberAJTR0046684
Pages (from-to)926-939
Number of pages14
JournalAmerican Journal of Translational Research
Volume9
Issue number3
StatePublished - 2017

Keywords

  • Aluminum
  • Glutathione
  • Oxaliplatin
  • Peripheral neuropathy
  • TRPA1

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