Antioxidant Effects of DPP-4 Inhibitors in Early Stages of Experimental Diabetic Retinopathy
Ramos, Hugo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bogdanov, Patricia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Huerta, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Deàs-Just, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández, Cristina (Universitat Autònoma de Barcelona. Departament de Medicina)
Simó Canonge, Rafael (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2022
Resum:	Hyperglycemia-induced oxidative stress plays a key role in the impairment of the retinal neurovascular unit, an early event in the pathogenesis of DR. The aim of this study was to assess the antioxidant properties of topical administration (eye drops) of sitagliptin in the diabetic retina. For this purpose, db/db mice received sitagliptin or vehicle eye drops twice per day for two weeks. Age-matched db/+ mice were used as the control group. We evaluated retinal mRNA (RT-PCR) and protein levels (Western blotting and immunohistochemistry) of different components from both the antioxidant system (NRF2, CAT, GPX, GR, CuZnSOD, and MnSOD) and the prooxidant machinery (PKC and TXNIP). We also studied superoxide levels (dihydroethidium staining) and oxidative damage to DNA/RNA (8-hydroxyguanosine immunostaining) and proteins (nitrotyrosine immunostaining). Finally, NF-кB translocation and IL-1β production were assessed through Western blotting and/or immunohistochemistry. We found that sitagliptin protected against diabetes-induced oxidative stress by reducing superoxide, TXNIP, PKC, and DNA/RNA/protein oxidative damage, and it prevented the downregulation of NRF2 and antioxidant enzymes, with the exception of catalase. Sitagliptin also exerted anti-inflammatory effects, avoiding both NF-кB translocation and IL-1β production. Sitagliptin prevents the diabetes-induced imbalance between ROS production and antioxidant defenses that occurs in diabetic retinas.
Ajuts:	Agencia Estatal de Investigación PID2019-104225RB-I00 Instituto de Salud Carlos III PI19/01215 Instituto de Salud Carlos III ICI20/00129
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:	Diabetes ; Diabetic retinopathy ; Sitagliptin ; Dipeptidyl peptidase-4 ; DPP-4 inhibitors ; Oxidative stress ; Antioxidant ; NRF2
Publicat a:	Antioxidants, Vol. 11, Num. 7 (july 2022) , ISSN 2076-3921

DOI: 10.3390/antiox11071418
PMID: 35883908

17 p, 7.9 MB

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