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Papers of the Week

Papers: 22 Jun 2019 - 28 Jun 2019

Animal Studies, Pharmacology/Drug Development

2019 Nov

Neurotox Res



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


Pontes R B, Lisboa M R P, Pereira A F, Lino J A, de Oliveira F F B, de Mesquita A K V, de Freitas Alves B W, Lima-Júnior R C P, Vale M L
Neurotox Res. 2019 Nov; 36(4):688-699.
PMID: 31228092.


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.