Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
Bogdanov, Patricia (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Ramos, Hugo (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Valeri, Marta (Hospital Universitari Vall d'Hebron)
Deàs-Just, Anna (Hospital Universitari Vall d'Hebron)
Huerta, Jordi (Hospital Universitari Vall d'Hebron)
Simó Canonge, Rafael (Universitat Autònoma de Barcelona. Departament de Medicina)
Hernández, Cristina (Universitat Autònoma de Barcelona. Departament de Medicina)
Data: |
2022 |
Resum: |
The neurovascular unit (NVU) plays an essential role in the development of diabetic retinopathy (DR). We previously reported that the topical administration (eye drops) of sitagliptin and saxagliptin, two dipeptidyl peptidase-4 inhibitors (DPP-4i), prevents retinal neurodegeneration and vascular leakage in db/db mice. The aim of the present study is to evaluate the minimum effective dose of the topical administration of these DPP-4i. For this purpose, sitagliptin and saxagliptin were tested at different concentrations (sitagliptin: 1 mg/mL, 5 and 10 mg/mL, twice per day; saxagliptin: 1 and 10 mg/mL, once or twice per day) in db/db mice. As end points of efficacy, the hallmarks of NVU impairment were evaluated: reactive gliosis, neural apoptosis, and vascular leakage. These parameters were assessed by immunohistochemistry, cell counting, and the Evans blue method, respectively. Our results demonstrated that the minimum effective dose is 5 mg/mL twice per day for sitagliptin, and 10 mg/mL twice per day for saxagliptin. In conclusion, this study provides useful results for the design of future preclinical regulatory studies and for planning clinical trials. |
Drets: |
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. |
Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Diabetic retinopathy ;
Dipeptidyl peptidase-4 inhibitors ;
Sitagliptin ;
Saxagliptin ;
Neurovascular unit ;
Retinal neurodegeneration ;
Experimental diabetes ;
Db/db mice |
Publicat a: |
Biomedicines, Vol. 10 (february 2022) , ISSN 2227-9059 |
DOI: 10.3390/biomedicines10020465
PMID: 35203674
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Registre creat el 2022-04-26, darrera modificació el 2024-05-22