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内皮素受体在奥沙利铂诱导的小鼠周围感觉神经病变中的作用。

Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice.

机构信息

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.

出版信息

Neurotox Res. 2019 Nov;36(4):688-699. doi: 10.1007/s12640-019-00074-2. Epub 2019 Jun 21.


DOI:10.1007/s12640-019-00074-2
PMID:31228092
Abstract

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.

摘要

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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本文引用的文献

[1]
Preventive Effects of Renin-angiotensin System Inhibitors on Oxaliplatin-induced Peripheral Neuropathy: A Retrospective Observational Study.

Clin Ther. 2018-7-23

[2]
Neurotoxic effect of oxaliplatin: Comparison with its oxalate-free analogue cis-[PtII(1R,2R-DACH)(3-acetoxy-1,1-cyclobutanedicarboxylato)] (LLC-1402) in mice.

Toxicol Appl Pharmacol. 2018-1-4

[3]
Bradykinin system is involved in endometriosis-related pain through endothelin-1 production.

Eur J Pain. 2017-10-16

[4]
Endothelin-1 Decreases Excitability of the Dorsal Root Ganglion Neurons via ET Receptor.

Mol Neurobiol. 2017-6-16

[5]
The effects of endothelin-1 on satellite glial cells in peripheral ganglia.

Neuropeptides. 2017-6

[6]
Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ.

Cancer Res. 2017-5-1

[7]
Neuropathic pain induced by spinal cord injury: Role of endothelin ETA and ETB receptors.

Neurosci Lett. 2016-3-23

[8]
Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice.

Naunyn Schmiedebergs Arch Pharmacol. 2015-11

[9]
Intraganglionic interactions between satellite cells and adult sensory neurons.

Mol Cell Neurosci. 2015-7

[10]
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J Pain Res. 2014-8-30

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