دورية أكاديمية
Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ.
| العنوان: | Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ. |
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| المؤلفون: | Elkholy SE; Department of Clinical Pharmacology, Faculty of Medicine, Port-Said University, Port-Said, Egypt., Elaidy SM; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt., El-Sherbeeny NA; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: nagla_elsherbeeny@med.suez.edu.eg., Toraih EA; Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Center of Excellence of Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt., El-Gawly HW; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. |
| المصدر: | Life sciences [Life Sci] 2020 Jun 01; Vol. 250, pp. 117557. Date of Electronic Publication: 2020 Mar 14. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Diabetic Neuropathies/*drug therapy , NAV1.7 Voltage-Gated Sodium Channel/*metabolism , Neuroprotective Agents/*therapeutic use , PPAR gamma/*metabolism , Pioglitazone/*therapeutic use , Ranolazine/*therapeutic use, Animals ; Behavior, Animal ; Comorbidity ; Diabetes Mellitus, Experimental/drug therapy ; Diet, High-Fat ; Hyperalgesia ; Inflammation/drug therapy ; Interleukin-1beta/metabolism ; Male ; Rats ; Rats, Wistar ; Spinal Cord/metabolism ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | Diabetic neuropathy (DN) is a common complication of diabetes mellitus (DM). Pathophysiology of DN includes inflammation and changes in expression and function of voltage-gated sodium channels (Nav) in peripheral nerves; and central reduction of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) expression. Aim: This study explored the effect of ranolazine (RN) versus pioglitazone (PIO) in DN induced in rats. The role of sciatic interleukin (IL)-1β, tumor necrosis factor-alpha (TNF)-α, Nav1.7, and spinal PPAR-γ expressions were determined. Materials and Methods: For induction of Type-2 DM, 40 high fat diet-fed rats were challenged by a single dose of intraperitoneal streptozotocin (30 mg/kg). One week later, oral PIO (10 mg/kg; once daily) or RN (20, 50 and 100 mg/kg; twice daily) were administered for six weeks. Weekly body weight and fasting blood sugar (FBS) were measured. Rats were tested for thermal hyperalgesia and mechanical allodynia. At the end of the experiment, sciatic nerves homogenates were examined for TNF-α and IL-1B levels, and Nav1.7 channel expression. Segments of spinal cords were investigated for the PPAR-γ gene expression. Evaluation of histopathology of sciatic nerves and spinal cords were done. Key Findings: In diabetic rats, PIO and RN individually improved evoked-pain behaviors, reduced sciatic TNF-α and 1L-1B levels; downregulated expressional levels of Nav1.7 channels; and increased the spinal PPAR-γ gene expression. RN in the dose of 100 mg/kg/day showed the most advantageous effects. Significance: RN has neuroprotective effects in Type-2 diabetes-induced DN. Further studies of combined RN-PIO treatment are recommended, especially in diabetic patients with cardiovascular co-morbidity. Competing Interests: Declaration of competing interest The authors declare no conflict of interest. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Diabetic neuropathy; Nav1.7 channel; PPAR-γ; Ranolazine; Type 2 diabetes |
| المشرفين على المادة: | 0 (IL1B protein, rat) 0 (Interleukin-1beta) 0 (NAV1.7 Voltage-Gated Sodium Channel) 0 (Neuroprotective Agents) 0 (PPAR gamma) 0 (Scn9a protein, rat) 0 (Tumor Necrosis Factor-alpha) A6IEZ5M406 (Ranolazine) X4OV71U42S (Pioglitazone) |
| تواريخ الأحداث: | Date Created: 20200319 Date Completed: 20200505 Latest Revision: 20200505 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.lfs.2020.117557 |
| PMID: | 32184124 |
| قاعدة البيانات: | MEDLINE |
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