The inhibitory effects of cobalt protoporphyrin IX and cannabinoid 2 receptor agonists in type 2 diabetic mice
McDonnell, Christina (Universitat Autònoma de Barcelona. Institut de Neurociències)
Leánez, Sergi (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pol, Olga (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	The activation of the transcription factor Nrf2 inhibits neuropathy and modulates the activity of delta-opioid receptors (DOR) in type 2 diabetic mice but the impact of Nrf2/HO-1 pathway on the antinociceptive actions of cannabinoid 2 receptors (CB2R) has not been assessed. Using male mice BKS. Cg-m+/+Leprdb/J (db/db) we investigated if treatment with cobalt protoporphyrin IX (CoPP), an HO-1 inductor, inhibited mechanical allodynia, hyperglycemia and obesity associated to type 2 diabetes. The antinociceptive effects of JWH-015 and JWH-133 (CB2R agonists) administered with and without CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, have been also evaluated. The expression of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1) and c-Jun N-terminal kinase (JNK) in sciatic nerve and that of the CB2R on the dorsal root ganglia from animals treated with CoPP and/or SFN were assessed. CoPP treatment inhibited allodynia, hyperglycemia and body weight gain in db/db mice by enhancing HO-1/NQO1 levels and reducing JNK phosphorylation. Both CoPP and SFN improved the antiallodynic effects of JWH-015 and JWH-133 and expression of CB2R in db/db mice. Therefore, we concluded that the activation of antioxidant Nrf2/HO-1 pathway potentiate the effects of CB2R agonists and might be suitable for the treatment of painful neuropathy linked to type 2 diabetes.
Grants:	Ministerio de Economía y Competitividad PS0900968 Ministerio de Economía y Competitividad PI1400927
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	International journal of molecular sciences, Vol. 18 Núm. 11 (november 2017) , p. 2268, ISSN 1422-0067

DOI: 10.3390/ijms18112268
PMID: 29143802

13 p, 2.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles