PloS one, 2017-07, Vol.12 (7), p.e0180998-e0180998
2017
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- The induction of the transcription factor Nrf2 enhances the antinociceptive effects of delta-opioid receptors in diabetic mice
- Ist Teil von
- PloS one, 2017-07, Vol.12 (7), p.e0180998-e0180998
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The involvement of heme oxygenase 1 (HO-1) in the modulation of the antinociceptive effects of opioids in type 1 diabetes has been demonstrated but the role played by the transcription factor Nrf2 in the regulation of painful neuropathy and in the effects and expression of δ-opioid receptors (DOR) in type 2 diabetes, has not been studied. In male BKS.Cg-m+/+Leprdb/J (db/db) mice, the anti-allodynic effects produced by a Nrf2 transcription factor activator, sulforaphane (SFN) administered alone and combined with two DOR agonists, [d-Pen(2),d-Pen(5)]-Enkephalin (DPDPE) and (+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N diethylbenzamide (SNC-80), were evaluated. The effects of SFN on glucose levels and body weight as well as on the proteins levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), MAPKs (JNK) and DOR in sciatic nerve from db/db mice were also assessed. This study showed that the administration of SFN dose dependently reversed mechanical allodynia, reduced hyperglycemia and body weight gain associated to type 2 diabetes and significantly increased the anti-allodynic effects of DPDPE and SNC-80 in db/db mice. This treatment normalized the down regulation of Nrf2 and NQO1 and enhanced the protein levels of HO-1 in db/db mice. Moreover, the administration of SFN also inhibited the JNK phosphorylation and DOR down-regulation in the sciatic nerve of diabetic mice. Our data indicated that SFN treatment is effective in reversing mechanical allodynia and enhancing DOR antinociceptive effects in db/db mice which effects might be mediated by activating Nrf2 signaling, reducing hyperglycemia, inhibiting JNK phosphorylation and avoiding DOR down-regulation in the sciatic nerve of these animals. These results propose SFN, alone and/or combined with DOR agonists, as interesting approaches for the treatment of painful diabetic neuropathy associated to type 2 diabetes in mice.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0180998Titel-ID: cdi_plos_journals_1917697016
- Format
- –
- Schlagworte
- Analysis, Animals, Benzamides - pharmacology, Biology and Life Sciences, Blood Glucose - drug effects, Blood Glucose - metabolism, Blotting, Western, Body weight, Body Weight - drug effects, Body Weight - genetics, Body Weight - physiology, Body weight gain, Cell cycle, Cytokinins, Diabetes, Diabetes mellitus, Diabetes Mellitus, Experimental - genetics, Diabetes Mellitus, Experimental - metabolism, Diabetes Mellitus, Type 2 - genetics, Diabetes Mellitus, Type 2 - metabolism, Diabetic Neuropathies - metabolism, Diabetic neuropathy, Down-regulation, Enkephalin, D-Penicillamine (2,5)- - pharmacology, Enkephalins, Enzymes, Glucose, Health aspects, Heme, Hyperalgesia - metabolism, Hyperglycemia, Inflammation, Inhibition, Insulin, Isothiocyanates - pharmacology, JNK protein, Kinases, Laboratory animals, Male, Medicine and Health Sciences, Mice, NAD, Narcotics, Neuropathy, NF-E2-Related Factor 2 - genetics, NF-E2-Related Factor 2 - metabolism, Obesity, Opioid receptors (type delta), Oxidative stress, Oxidoreductase, Oxygenase, Pain, Pain perception, Phosphorylation, Piperazines - pharmacology, Proteins, Quinone, Quinone oxidoreductase, Receptors, Receptors, Opioid, delta - agonists, Receptors, Opioid, delta - genetics, Receptors, Opioid, delta - metabolism, Regulations, Research and Analysis Methods, Reversing, Risk factors, Rodents, Sciatic nerve, Sulforafan, Sulforaphane, Transcription factors, Weight reduction