Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats

Reactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effe...

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Main Authors: Naohiro Iwata, Naoto Ogawa, Tom Imai, Siti Sabirah Binti Ridzuan, Shinya Kamiuchi, Hirokazu Matsuzaki, Meiyan Xuan, Bo Yuan, Mari Okazaki, Yasuhide Hibino
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Language:English
Published: MDPI AG 2025-06-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/7/773
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author Naohiro Iwata
Naoto Ogawa
Tom Imai
Siti Sabirah Binti Ridzuan
Shinya Kamiuchi
Hirokazu Matsuzaki
Meiyan Xuan
Bo Yuan
Mari Okazaki
Yasuhide Hibino
author_facet Naohiro Iwata
Naoto Ogawa
Tom Imai
Siti Sabirah Binti Ridzuan
Shinya Kamiuchi
Hirokazu Matsuzaki
Meiyan Xuan
Bo Yuan
Mari Okazaki
Yasuhide Hibino
author_sort Naohiro Iwata
collection DOAJ
description Reactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effects against ischemic brain injury. ODS rats were given an AA-free diet (0% AA), 0.1% AA, or 1% AA in drinking water for two weeks before undergoing middle cerebral artery occlusion and reperfusion (MCAO/Re). The 0% AA group exhibited pronounced damage following MCAO/Re, characterized by the induction of lipid peroxidation, O<sub>2</sub><sup>−</sup> production, inflammation-related gene expression, and extensive infarct formation. In contrast, the 1% AA group showed reductions in these markers, along with fewer TUNEL-positive cells and a smaller infarct volume. Notably, sodium-dependent vitamin C transporter 2 (SVCT2) expression increased in both two AA-supplemented groups, although the 0.1% AA group did not exhibit sufficient improvement in post-ischemic damage. A two-week intake of AA significantly alleviated MCAO/Re-mediated injuries associated with oxidative stress and inflammation in ODS rats. Sufficient AA intake is thus supposed to mitigate ischemic damage, possibly through SVCT2 upregulation and enhanced AA availability, leading to the suppression of oxidative stress and inflammation.
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spelling doaj-art-2a67302aad854fb2a960d147429b90f92025-08-20T02:48:19ZengMDPI AGAntioxidants2076-39212025-06-0114777310.3390/antiox14070773Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS RatsNaohiro Iwata0Naoto Ogawa1Tom Imai2Siti Sabirah Binti Ridzuan3Shinya Kamiuchi4Hirokazu Matsuzaki5Meiyan Xuan6Bo Yuan7Mari Okazaki8Yasuhide Hibino9Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanLaboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, JapanReactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effects against ischemic brain injury. ODS rats were given an AA-free diet (0% AA), 0.1% AA, or 1% AA in drinking water for two weeks before undergoing middle cerebral artery occlusion and reperfusion (MCAO/Re). The 0% AA group exhibited pronounced damage following MCAO/Re, characterized by the induction of lipid peroxidation, O<sub>2</sub><sup>−</sup> production, inflammation-related gene expression, and extensive infarct formation. In contrast, the 1% AA group showed reductions in these markers, along with fewer TUNEL-positive cells and a smaller infarct volume. Notably, sodium-dependent vitamin C transporter 2 (SVCT2) expression increased in both two AA-supplemented groups, although the 0.1% AA group did not exhibit sufficient improvement in post-ischemic damage. A two-week intake of AA significantly alleviated MCAO/Re-mediated injuries associated with oxidative stress and inflammation in ODS rats. Sufficient AA intake is thus supposed to mitigate ischemic damage, possibly through SVCT2 upregulation and enhanced AA availability, leading to the suppression of oxidative stress and inflammation.https://www.mdpi.com/2076-3921/14/7/773L-ascorbic acid (AA)osteogenic disorder Shionogi (ODS) ratmiddle cerebral artery occlusion and reperfusion (MCAO/Re)reactive oxygen species (ROS)neuronal apoptosispro-inflammatory cytokines
spellingShingle Naohiro Iwata
Naoto Ogawa
Tom Imai
Siti Sabirah Binti Ridzuan
Shinya Kamiuchi
Hirokazu Matsuzaki
Meiyan Xuan
Bo Yuan
Mari Okazaki
Yasuhide Hibino
Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
Antioxidants
L-ascorbic acid (AA)
osteogenic disorder Shionogi (ODS) rat
middle cerebral artery occlusion and reperfusion (MCAO/Re)
reactive oxygen species (ROS)
neuronal apoptosis
pro-inflammatory cytokines
title Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
title_full Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
title_fullStr Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
title_full_unstemmed Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
title_short Administration of Ascorbic Acid Alleviates Neuronal Damage After Cerebral Ischemia in ODS Rats
title_sort administration of ascorbic acid alleviates neuronal damage after cerebral ischemia in ods rats
topic L-ascorbic acid (AA)
osteogenic disorder Shionogi (ODS) rat
middle cerebral artery occlusion and reperfusion (MCAO/Re)
reactive oxygen species (ROS)
neuronal apoptosis
pro-inflammatory cytokines
url https://www.mdpi.com/2076-3921/14/7/773
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