Abstract
Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced cold allodynia in rats and the mechanisms involved. A single oxaliplatin injection (6 mg/kg, i.p.) induced significant cold allodynia signs based on tail immersion tests using cold water (4 °C). Daily oral administration of water extract of C. Cortex (WECC) (100, 200, and 400 mg/kg) for five consecutive days following an oxaliplatin injection dose-dependently alleviated cold allodynia with only a slight difference in efficacies between the middle dose at 200 mg/kg and the highest dose at 400 mg/kg. WECC at 200 mg/kg significantly suppressed the activation of astrocytes and microglia and decreased the expression levels of IL-1β and TNF in the spinal cord after injection with oxaliplatin. Furthermore, oral administration of coumarin (10 mg/kg), a major phytocompound of C. Cortex, markedly reduced cold allodynia. These results indicate that C. Cortex has a potent anti-allodynic effect in oxaliplatin-injected rats through inhibiting spinal glial cells and pro-inflammatory cytokines. We also suggest that coumarin might play a role in the anti-allodynic effect of C. Cortex.
Highlights
Oxaliplatin, a third-generation platinum-based chemotherapy drug, displays anti-tumor activity against a wide range of tumors, including ovarian, breast, lung, and advanced colorectal cancers [1,2,3].Unlike other platinum compounds, oxaliplatin rarely exhibits nephrotoxicity or hematotoxicity [4]
Behavioral tests were performed before oxaliplatin injection and every 24 h after the administration of water extract of C. Cortex (WECC)
24–48 h the oxaliplatin injection. This side effect can limit the use of this drug and lead to cessation of to following the oxaliplatin injection [25,26]
Summary
Oxaliplatin, a third-generation platinum-based chemotherapy drug, displays anti-tumor activity against a wide range of tumors, including ovarian, breast, lung, and advanced colorectal cancers [1,2,3]. Unlike other platinum compounds (e.g., cisplatin and carboplatin), oxaliplatin rarely exhibits nephrotoxicity or hematotoxicity [4]. Even a single injection of oxaliplatin can cause peripheral neuropathy manifesting as paresthesia and dysesthesia in the extremities. This peripheral neuropathy can be triggered or enhanced by exposure to cold [5,6]. Molecules 2016, 21, 1253 in oxaliplatin-induced peripheral neuropathy remains unclear. An effective treatment method for neuropathic allodynia needs to be developed [7]
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