Department of Physical Therapy, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-160, Brazil.
Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-170, Brazil.
Neurotox Res. 2019 Nov;36(4):688-699. doi: 10.1007/s12640-019-00074-2. Epub 2019 Jun 21.
The aim of this study was to evaluate the participation of the endothelin ET and ET receptors and the effects of bosentan in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice. Adult male Swiss mice received 1 mg/kg of oxaliplatin intravenously, twice a week for 5 weeks. Dorsal root ganglia (DRG) and spinal cords were removed for evaluation of the endothelin ET and ET receptor expression. Afterwards, selective (BQ-123 and BQ-788; 10 nmol in 30 μL, intraplantarly) and non-selective (bosentan, 100 mg/kg, orally) antagonists were administered in order to evaluate the involvement of the endothelin receptors in OIN. Mechanical and thermal nociception tests were performed once a week for 56 days. Oxaliplatin induced mechanical and thermal hypersensitivity and increased the endothelin ET receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ET receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ET and ET receptor selective antagonists partially prevented mechanical hyperalgesia in mice with OIN (P < 0.05). Moreover, bosentan prevented mechanical and thermal hypersensitivity in oxaliplatin-treated mice (P < 0.05). In conclusion, both endothelin ET and ET receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.
本研究旨在评估内皮素 ET 和 ET 受体在奥沙利铂诱导的周围感觉神经病 (OIN) 中的作用以及 bosentan 的影响。成年雄性瑞士小鼠每周两次静脉注射 1mg/kg 的奥沙利铂,共 5 周。取出背根神经节 (DRG) 和脊髓以评估内皮素 ET 和 ET 受体的表达。随后,给予选择性(BQ-123 和 BQ-788;10nmol 在 30μL 中,足底内注射)和非选择性(bosentan,100mg/kg,口服)拮抗剂,以评估内皮素受体在 OIN 中的参与情况。每周进行一次机械和热痛觉测试,共 56 天。奥沙利铂诱导机械和热敏性,并增加 DRG 和脊髓中的内皮素 ET 受体表达(P<0.05)。内皮素 ET 受体表达在 DRG 中增加(P<0.05),但在脊髓中没有增加。内皮素 ET 和 ET 受体选择性拮抗剂均可部分预防 OIN 小鼠的机械性痛觉过敏(P<0.05)。此外,bosentan 可预防奥沙利铂处理的小鼠的机械性和热敏性(P<0.05)。总之,内皮素 ET 和 ET 受体似乎都参与了 OIN,它们可能是管理这种临床特征的潜在靶点。
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