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| Página principal > Artículos > Artículos publicados > Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice |
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Institut de Neurociències)
| Fecha: | 2018 |
| Resumen: | The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i. e. , the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1 expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1. 4-fold vs. Ctrl, ∼ 1. 3- fold vs. Stz-vehicle; p < 0. 05) and was attributed to significant elevations in both non-HDL (∼ 1. 8-fold vs. Ctrl; ∼ 1. 6-fold vs. Stz-vehicle; p < 0. 05) and HDL cholesterol (∼ 1. 3-fold vs. Ctrl, ∼ 1. 2-fold vs. Stz-vehicle; p < 0. 05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [ 3 H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice. |
| Ayudas: | Ministerio de Economía, Industria y Competitividad PI17/00232 Ministerio de Economía, Industria y Competitividad PI16/00139 Ministerio de Economía, Industria y Competitividad PI16/00471 Ministerio de Economía, Industria y Competitividad PI0900968 Ministerio de Economía, Industria y Competitividad PI1400927 Instituto de Salud Carlos III CP13/00070 Agència de Gestió d'Ajuts Universitaris i de Recerca FI-DGR2014 |
| Nota: | Altres ajuts: La Marató grant number 201602-31 to JJ. |
| Derechos: | 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.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Publicado en: | PloS one, Vol. 13 (october 2018) , ISSN 1932-6203 |
