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Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model

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 lea...

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Autores principales: Bogdanov, Patricia, Ramos, Hugo, Valeri, Marta, Deàs-Just, Anna, Huerta, Jordi, Simó, Rafael, Hernández, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962353/
https://www.ncbi.nlm.nih.gov/pubmed/35203674
http://dx.doi.org/10.3390/biomedicines10020465
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author Bogdanov, Patricia
Ramos, Hugo
Valeri, Marta
Deàs-Just, Anna
Huerta, Jordi
Simó, Rafael
Hernández, Cristina
author_facet Bogdanov, Patricia
Ramos, Hugo
Valeri, Marta
Deàs-Just, Anna
Huerta, Jordi
Simó, Rafael
Hernández, Cristina
author_sort Bogdanov, Patricia
collection PubMed
description 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.
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spelling pubmed-89623532022-03-30 Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model Bogdanov, Patricia Ramos, Hugo Valeri, Marta Deàs-Just, Anna Huerta, Jordi Simó, Rafael Hernández, Cristina Biomedicines Article 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. MDPI 2022-02-16 /pmc/articles/PMC8962353/ /pubmed/35203674 http://dx.doi.org/10.3390/biomedicines10020465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bogdanov, Patricia
Ramos, Hugo
Valeri, Marta
Deàs-Just, Anna
Huerta, Jordi
Simó, Rafael
Hernández, Cristina
Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title_full Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title_fullStr Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title_full_unstemmed Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title_short Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
title_sort minimum effective dose of dpp-4 inhibitors for treating early stages of diabetic retinopathy in an experimental model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962353/
https://www.ncbi.nlm.nih.gov/pubmed/35203674
http://dx.doi.org/10.3390/biomedicines10020465
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