Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System

Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destr...

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Main Authors: Govinda Bhattarai, Han-Sol So, Thi Thu Trang Kieu, Sung-Ho Kook, Jeong-Chae Lee, Young-Mi Jeon
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/13/10/3575
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author Govinda Bhattarai
Han-Sol So
Thi Thu Trang Kieu
Sung-Ho Kook
Jeong-Chae Lee
Young-Mi Jeon
author_facet Govinda Bhattarai
Han-Sol So
Thi Thu Trang Kieu
Sung-Ho Kook
Jeong-Chae Lee
Young-Mi Jeon
author_sort Govinda Bhattarai
collection DOAJ
description Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1β in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.
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spelling doaj.art-c8ca63ff9bfe42f8b83014d006ad9e582023-11-22T19:30:44ZengMDPI AGNutrients2072-66432021-10-011310357510.3390/nu13103575Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant SystemGovinda Bhattarai0Han-Sol So1Thi Thu Trang Kieu2Sung-Ho Kook3Jeong-Chae Lee4Young-Mi Jeon5Cluster for Craniofacial Development and Regeneration Research, School of Dentistry, Jeonbuk National University, Jeonju 54896, KoreaResearch Center of Bioactive Materials, Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, KoreaResearch Center of Bioactive Materials, Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, School of Dentistry, Jeonbuk National University, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, School of Dentistry, Jeonbuk National University, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, School of Dentistry, Jeonbuk National University, Jeonju 54896, KoreaNumerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1β in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.https://www.mdpi.com/2072-6643/13/10/3575astaxanthindiabetesperiodontal destructionoxidative damagehyperglycemic complicationNrf2 pathway
spellingShingle Govinda Bhattarai
Han-Sol So
Thi Thu Trang Kieu
Sung-Ho Kook
Jeong-Chae Lee
Young-Mi Jeon
Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
Nutrients
astaxanthin
diabetes
periodontal destruction
oxidative damage
hyperglycemic complication
Nrf2 pathway
title Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
title_full Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
title_fullStr Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
title_full_unstemmed Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
title_short Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System
title_sort astaxanthin inhibits diabetes triggered periodontal destruction ameliorates oxidative complications in stz injected mice and recovers nrf2 dependent antioxidant system
topic astaxanthin
diabetes
periodontal destruction
oxidative damage
hyperglycemic complication
Nrf2 pathway
url https://www.mdpi.com/2072-6643/13/10/3575
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