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

Abstract

The aim of this study was to evaluate the participation of the endothelin ETA and ETB 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 ETA and ETB 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 ETA receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ETB receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ETA and ETB 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 ETA and ETB receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.

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  • Authors+Show Affiliations

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    Department of Physical Therapy, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-160, Brazil.

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    Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-170, Brazil.

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    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará (UFC), R. Cel. Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, CE, 60430-270, Brazil.

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    Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-140, Brazil.

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    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará (UFC), R. Cel. Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, CE, 60430-270, Brazil.

    ,

    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.

    ,

    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará (UFC), R. Cel. Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, CE, 60430-270, Brazil.

    Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-170, Brazil. marianavale@yahoo.com. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará (UFC), R. Cel. Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, CE, 60430-270, Brazil. marianavale@yahoo.com.

    Source

    Neurotoxicity research : 2019 Jun 21 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31228092

    Citation

    Pontes, Renata Bessa, et al. "Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced By Oxaliplatin in Mice." Neurotoxicity Research, 2019.
    Pontes RB, Lisboa MRP, Pereira AF, et al. Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice. Neurotox Res. 2019.
    Pontes, R. B., Lisboa, M. R. P., Pereira, A. F., Lino, J. A., de Oliveira, F. F. B., de Mesquita, A. K. V., ... Vale, M. L. (2019). Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice. Neurotoxicity Research, doi:10.1007/s12640-019-00074-2.
    Pontes RB, et al. Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced By Oxaliplatin in Mice. Neurotox Res. 2019 Jun 21; PubMed PMID: 31228092.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Involvement of Endothelin Receptors in Peripheral Sensory Neuropathy Induced by Oxaliplatin in Mice. AU - Pontes,Renata Bessa, AU - Lisboa,Mario Roberto Pontes, AU - Pereira,Anamaria Falcão, AU - Lino,Juliana Arcanjo, AU - de Oliveira,Francisco Fábio Bezerra, AU - de Mesquita,Aline Kelly Viana, AU - de Freitas Alves,Bruno Wesley, AU - Lima-Júnior,Roberto César Pereira, AU - Vale,Mariana Lima, Y1 - 2019/06/21/ PY - 2018/09/12/received PY - 2019/06/11/accepted PY - 2019/05/24/revised PY - 2019/6/23/entrez KW - Endothelin receptors KW - Neuropathic pain KW - Oxaliplatin KW - Pain JF - Neurotoxicity research JO - Neurotox Res N2 - The aim of this study was to evaluate the participation of the endothelin ETA and ETB 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 ETA and ETB 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 ETA receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ETB receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ETA and ETB 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 ETA and ETB receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/31228092/Involvement_of_Endothelin_Receptors_in_Peripheral_Sensory_Neuropathy_Induced_by_Oxaliplatin_in_Mice L2 - https://dx.doi.org/10.1007/s12640-019-00074-2 DB - PRIME DP - Unbound Medicine ER -