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.

Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes

“…Our work does not rule out the possibility that occlusal injury of the db/db group versus the control group plays a role in inflammatory outcomes. However, previous work from our laboratory (Zhao et al 2021) and many others (Bhattarai et al 2021) indicate that hyperglycemia has a much stronger effect on inflammation than does occlusal trauma in diabetic mice, the latter a condition that is not echoed in typical models of streptozocin-induced diabetic mice. Because of the differences between mouse and human gingiva, the db/db model only partially recapitulates the pathological complexity of patients with T2D, and further research will be valuable on translating this information in humans.…”

Pathogenic Molecular Mechanisms in Periodontitis and Peri-Implantitis: Role of Advanced Glycation End Products

“…Apart from AG and PTB, vitamin C administration decreased AGE-positive cells, which were abundant in periodontal and diabetic subjects [17]. In a similar way, astraxanthin effectively upregulated the Nrf2 signaling pathway, counteracted the oxidative stress that was attributed to AGEs, and enhanced osteogenesis of hPDLCs in vivo [84]. In this way, the Nrf2 pathway offers an indirect, alternative option to confront the detrimental effects of high glucose levels on the periodontium.…”

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

“…It should be noted, however, that it is unclear whether this is a canonical pathway via dissociation of Keap1 or the result of some indirect non-canonical activation pathway. Indeed, AX increases the expression of Nrf2 in certain pathological models and in certain tissues [ 92 , 101 , 102 ]. Unfortunately, most studies investigating the effect of AX on Nrf2 activation did not examine downstream gene expression, including the targets of Nrf2, such as the glutamate-cysteine ligase catalytic subunit gene ( Gclc in rodents, GCLC in human) and the NAD(P)H:quinone oxidoreductase-1 gene ( Nqo1 in rodents, NQO1 in human).…”