Neuroprotective Effect of 3',4'-Dihydroxyphenylglycol in Type-1-like Diabetic Rats-Influence of the Hydroxytyrosol/3',4'-dihydroxyphenylglycol Ratio.

María Dolores Rodríguez-Pérez,Esther Martín-Aurioles,Cristina Verdugo,José Pedro De La Cruz,María Monsalud Arrebola,Inmaculada Pérez De Algaba,Laura Ortega-Hombrados,María África Fernández-Prior,Alejandra Bermúdez-Oria,José Antonio González-Correa

doi:10.3390/nu14061146

Abstract

The aim of this study was to assess the possible neuroprotective effect of 3′,4′-dihydroxyphenylglycol (DHPG), a polyphenol from extra virgin olive oil (EVOO), in an experimental model of diabetes and whether this effect is modified by the presence of another EVOO polyphenol, hydroxytyrosol (HT). The neuroprotective effect was assessed in a hypoxia–reoxygenation model in brain slices and by quantifying retinal nerve cells. The animals were distributed as follows: (1) normoglycemic rats (NDR), (2) diabetic rats (DR), (3) DR treated with HT (5 mg/kg/day p.o.), (4) DR treated with DHPG (0.5 mg/kg/day), or (5) with 1 mg/kg/day, (6) DR treated with HT plus DHPG 0.5 mg/kg/day, or (7) HT plus 1 mg/kg/day p.o. DHPG. Diabetic animals presented higher levels of oxidative stress variables and lower numbers of neuronal cells in retinal tissue. The administration of DHPG or HT reduced most of the oxidative stress variables and brain lactate dehydrogenase efflux (LDH) as an indirect index of cellular death and also reduced the loss of retinal cells. The association of DHPG+HT in the same proportions, as found in EVOO, improved the neuroprotective and antioxidant effects of both polyphenols.

Highlights

Introduction iationsIn the evolution of diabetes mellitus, controlling blood glucose levels serves to improve the metabolic profiles of patients and reduces the appearance and/or intensity of long-term cardiovascular complications [1]
We found no studies on the possible neuroprotective effects of DHPG after oral administration; this effect was only described in an in vitro study on the brain tissue of healthy rats [21], so it seemed interesting to determine if this effect could be reproduced in an experimental model of diabetes treated orally with DHPG and HT—alone or in association using the same proportions found in extra virgin olive oil (EVOO)
This study showed that DHPG exerts a neuroprotective effect in a rat model of type

Summary

Introduction

In the evolution of diabetes mellitus, controlling blood glucose levels serves to improve the metabolic profiles of patients and reduces the appearance and/or intensity of long-term cardiovascular complications [1]. Diabetic macroangiopathy does not differ from the arteriosclerosis process among the general population, it occurs earlier in time and is more intense in its vascular alterations, especially those of an ischemic nature [2]. Diabetic microangiopathy is typical of diabetes mellitus and can appear in the kidney (diabetic nephropathy), eye (diabetic retinopathy), or nervous tissue (diabetic neuropathy) [3]. Diabetic nervous tissue damage can occur in the peripheral nerves or in the central nervous system [4,5]. A greater sensitivity of the central nervous tissue to ischemic damage, independent of diabetic vascular alterations, was previously described in models of Licensee MDPI, Basel, Switzerland.

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