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

Abstract

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.

• Authors: Govinda Bhattarai, Han-Sol So, Thi Thu Trang Kieu, Sung-Ho Kook, Jeong-Chae Lee, Young-Mi Jeon
• Journal: Nutrients (Nutrients) Vol. 13 Issue 10 (Oct 12 2021) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 34684576 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Blood Glucose
• Cytokines
• Glycation End Products, Advanced
• Inflammation Mediators
• NF-E2-Related Factor 2
• Reactive Oxygen Species
• Xanthophylls
• Streptozocin
• astaxanthine
• Catalase
• Superoxide Dismutase

Topics

• Adolescent
• Alveolar Process (pathology)
• Animals
• Antioxidants (metabolism)
• Blood Glucose (metabolism)
• Catalase (blood)
• Cell Proliferation
• Cytokines (metabolism)
• DNA Damage
• Diabetes Mellitus, Experimental (blood, complications)
• Dietary Supplements
• Feeding Behavior
• Glycation End Products, Advanced (metabolism)
• Humans
• Hyperglycemia (complications)
• Inflammation Mediators (metabolism)
• Injections
• Lymphocytes (immunology)
• Male
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Osteoclasts (drug effects, pathology)
• Oxidative Stress
• Periodontal Ligament (pathology)
• Periodontitis (blood, drug therapy, etiology)
• Reactive Oxygen Species (metabolism)
• Streptozocin (administration & dosage)
• Superoxide Dismutase (blood)
• Up-Regulation
• Xanthophylls (pharmacology, therapeutic use)
• Young Adult
• Mice