Next Article in Journal
Telomeres and Telomerase in Hematopoietic Dysfunction: Prognostic Implications and Pharmacological Interventions
Next Article in Special Issue
Alterations in Rat Accumbens Endocannabinoid and GABA Content during Fentanyl Treatment: The Role of Ghrelin
Previous Article in Journal
Hungry Neurons: Metabolic Insights on Seizure Dynamics
Previous Article in Special Issue
Chronic Δ9-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain
Article

The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice

1
Grup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau, 08025 Barcelona, Spain
2
Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(11), 2268; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112268
Received: 29 September 2017 / Revised: 25 October 2017 / Accepted: 27 October 2017 / Published: 28 October 2017
(This article belongs to the Special Issue Cannabinoid Signaling in Nervous System)
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. View Full-Text
Keywords: antinociception; cannabinoid receptors; diabetic neuropathy; heme oxygenase 1; NAD(P)H: quinone oxidoreductase 1; Nrf2 transcription factor antinociception; cannabinoid receptors; diabetic neuropathy; heme oxygenase 1; NAD(P)H: quinone oxidoreductase 1; Nrf2 transcription factor
Show Figures

Figure 1

MDPI and ACS Style

McDonnell, C.; Leánez, S.; Pol, O. The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice. Int. J. Mol. Sci. 2017, 18, 2268. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112268

AMA Style

McDonnell C, Leánez S, Pol O. The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice. International Journal of Molecular Sciences. 2017; 18(11):2268. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112268

Chicago/Turabian Style

McDonnell, Christina, Sergi Leánez, and Olga Pol. 2017. "The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice" International Journal of Molecular Sciences 18, no. 11: 2268. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18112268

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop