57e94b4b0e889d72cc40ca905bf0239d ijms_a2017v18n11p2268.pdf d4997a453be96d1427cd06b0529f550388c37855 ijms_a2017v18n11p2268.pdf e8a6d7ccf024e10002addf7ed532799d6ccb14a7f206f931ad53be50c8673657 ijms_a2017v18n11p2268.pdf Title: The Inhibitory Effects of Cobalt Protoporphyrin IX and Cannabinoid 2 Receptor Agonists in Type 2 Diabetic Mice Subject: 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. Keywords: antinociception; cannabinoid receptors; diabetic neuropathy; heme oxygenase 1; NAD(P)H: quinone oxidoreductase 1; Nrf2 transcription factor Author: Christina McDonnell, Sergi Leánez and Olga Pol Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.17 CreationDate: Sat Oct 28 10:23:08 2017 CEST ModDate: Sat Oct 28 10:23:08 2017 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2773214 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XZXPAH+URWPalladioL-Ital Type 1 Custom yes yes no 98 0 OBEMTN+URWPalladioL-Bold Type 1 Custom yes yes no 99 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 100 0 OXBKYU+TeXGyreAdventor-Bold Type 1 Custom yes yes no 101 0 IUCFSL+URWPalladioL-Roma Type 1 Custom yes yes no 102 0 MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 103 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 108 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 109 0 OJYQXC+CMSY10 Type 1 Builtin yes yes no 153 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 179 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 180 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 181 0 Times New Roman TrueType WinAnsi no no no 182 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 199 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 200 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 201 0 Times New Roman TrueType WinAnsi no no no 202 0 IHZXYI+EURM10 Type 1 Builtin yes yes no 229 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 232 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 233 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 234 0 Times New Roman TrueType WinAnsi no no no 235 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 260 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 261 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 262 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 263 0 Times New Roman TrueType WinAnsi no no no 264 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 293 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 294 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 295 0 Times New Roman TrueType WinAnsi no no no 296 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 338 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 339 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 340 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 341 0 Times New Roman TrueType WinAnsi no no no 342 0 Jhove (Rel. 1.6, 2011-01-04) Date: 2019-02-14 18:15:34 CET RepresentationInformation: ijms_a2017v18n11p2268.pdf ReportingModule: BYTESTREAM, Rel. 1.3 (2007-04-10) LastModified: 2019-01-30 11:56:00 CET Size: 2773214 Format: bytestream Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/octet-stream Checksum: f4815226 Type: CRC32 Checksum: 57e94b4b0e889d72cc40ca905bf0239d Type: MD5 Checksum: d4997a453be96d1427cd06b0529f550388c37855 Type: SHA-1