Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice
| العنوان: | Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice |
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| المؤلفون: | Méndez-Lara K.A., Santos D., Farré N., Ruiz-Nogales S., Leánez S., Sánchez-Quesada J.L., Zapico E., Lerma E., Escola-Gil J.C., Blanco-Vaca F., Martón-Campos J.M., Julve J., Pol O. |
| المصدر: | PLoS One r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Bdkrb1 gene, cholesterol blood level, antioxidant activity, high density lipoprotein cholesterol, animal, drug, Cybb gene, diabetic neuropathy, unclassified drug, nociceptive pain, high density lipoprotein, histopathology, blood sampling, organometallic compound, oxidation, mouse model, animal experiment, drug administration, complication, macrophage, lipoprotein blood level, liver, insulin dependent diabetes mellitus, Article, animal tissue, in vivo study, male, blood, cholesterol transport, controlled study, gene, antilipemic agent, antinociception, mouse, allodynia, hyperalgesia, nonhuman, treatment duration, tricarbonyldichlororuthenium (II) dimer, streptozocin, animal model, dyslipidemia, cholesterol, antidiabetic agent, experimental behavioral test, feces, carbon monoxide releasing molecule tricarbonyldichlororuthenium 2, C57BL/6N mouse, gene expression, hyperglycemia, low density lipoprotein, streptozotocin-induced diabetes mellitus |
| الوصف: | 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 Bdkrb1expression) 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 [3H]-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. © 2018 Méndez-Lara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::3dc774149bfc7a95f39b7f57c443b1fc https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10236 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.RECOLECTA.....3dc774149bfc7a95f39b7f57c443b1fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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