Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1

Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1...

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Main Authors: Josué Rivera-Pérez, Martín Martínez-Rosas, César A. Conde-Castañón, Julia D. Toscano-Garibay, Nancy J. Ruiz-Pérez, Pedro L. Flores, Elvia Mera Jiménez, Javier Flores-Estrada
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/21/10/3716
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author Josué Rivera-Pérez
Martín Martínez-Rosas
César A. Conde-Castañón
Julia D. Toscano-Garibay
Nancy J. Ruiz-Pérez
Pedro L. Flores
Elvia Mera Jiménez
Javier Flores-Estrada
author_facet Josué Rivera-Pérez
Martín Martínez-Rosas
César A. Conde-Castañón
Julia D. Toscano-Garibay
Nancy J. Ruiz-Pérez
Pedro L. Flores
Elvia Mera Jiménez
Javier Flores-Estrada
author_sort Josué Rivera-Pérez
collection DOAJ
description Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with <i>Nrf2/Ho-1</i> expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0–30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the <i>Ho-1</i> mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including <i>Ho-1</i> mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of <i>Ho-1</i> expression.
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spelling doaj.art-2faa692bd19843ab91d49bd17287d94c2023-11-20T01:39:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110371610.3390/ijms21103716Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1Josué Rivera-Pérez0Martín Martínez-Rosas1César A. Conde-Castañón2Julia D. Toscano-Garibay3Nancy J. Ruiz-Pérez4Pedro L. Flores5Elvia Mera Jiménez6Javier Flores-Estrada7Instituto de Neurobiología, Universidad Nacional Autónoma de Mexico (UNAM), Campus UNAM-Juriquilla, CP 76230 Querétaro, MexicoDepartamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección 16, Tlalpan, CP 14080 Ciudad de Mexico, MexicoDepartamento de Oftalmología, Centro Médico Nacional La Raza, Paseo de las Jacarandas S/N, La Raza, Azcapotzalco, CP 02990 Ciudad de Mexico, MexicoDivisión de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, MexicoDivisión de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, MexicoDepartamento de Instrumentación Electromecánica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección 16, Tlalpan, CP 14080 Ciudad de Mexico, MexicoLaboratorio de Cultivo Celular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomas, Miguel Hidalgo, CP 11340 Ciudad de Mexico, MexicoDivisión de Investigación, Hospital Juárez de Mexico, Av. Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, CP 07760 Ciudad de Mexico, MexicoRetinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with <i>Nrf2/Ho-1</i> expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0–30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the <i>Ho-1</i> mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including <i>Ho-1</i> mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of <i>Ho-1</i> expression.https://www.mdpi.com/1422-0067/21/10/3716retinal ischemia/reperfusion (rI/R)epigallocatechin-3-gallate (EGCG)high-mobility group Box 1 (HMGB1)nuclear factor erythroid 2-related factor 2 (Nrf2)heme oxygenase-1 (HO-1)
spellingShingle Josué Rivera-Pérez
Martín Martínez-Rosas
César A. Conde-Castañón
Julia D. Toscano-Garibay
Nancy J. Ruiz-Pérez
Pedro L. Flores
Elvia Mera Jiménez
Javier Flores-Estrada
Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
International Journal of Molecular Sciences
retinal ischemia/reperfusion (rI/R)
epigallocatechin-3-gallate (EGCG)
high-mobility group Box 1 (HMGB1)
nuclear factor erythroid 2-related factor 2 (Nrf2)
heme oxygenase-1 (HO-1)
title Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
title_full Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
title_fullStr Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
title_full_unstemmed Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
title_short Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1
title_sort epigallocatechin 3 gallate has a neuroprotective effect in retinas of rabbits with ischemia reperfusion through the activation of nrf2 ho 1
topic retinal ischemia/reperfusion (rI/R)
epigallocatechin-3-gallate (EGCG)
high-mobility group Box 1 (HMGB1)
nuclear factor erythroid 2-related factor 2 (Nrf2)
heme oxygenase-1 (HO-1)
url https://www.mdpi.com/1422-0067/21/10/3716
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