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Astaxanthin inhibits oxidative stress and apoptosis in diabetic retinopathy
Affiliation:1. Department of Ophthalmology, Xinchang County People''s Hospital, Shaoxing City, Zhejiang Province 312500, China;2. School of Pharmacy, Hangzhou Medical College, Hangzhou City, Zhejiang Province 310059, China;1. Department of Anatomy, Physiology, and Theriogenology, College of Veterinary Medicine, University of Duhok, Duhok City, Kurdistan Region, Iraq;2. Department of Anatomy and Histology, College of Veterinary Medicine, University of Mosul, Mosul City, Iraq;1. Southwest Medical University, NO.1 Section 1, Xianglin Road, Luzhou City, Sichuan Province 646000, China;2. Department of Plastic and Burn Surgery, Affiliated Hospital of Southwest Medical University, National Key Clinical Construction Specialty, Wound Repair and Regeneration Laboratory, NO.25 Taiping Street, Jiangyang District, Luzhou 646000 Sichuan Province, China;1. Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Kar?owicza 24, 85-092 Bydgoszcz, Poland;2. Students Research Group of Cell Biology and Ultrastructure at Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland;1. Laboratory of Veterinary Anatomy and Cell Biology, Faculty of Agriculture, Iwate University, Morioka, Japan;2. Department of Anatomy (Cell Biology), Iwate Medical University, Yahaba, Japan
Abstract:BackgroundThe pathophysiology of diabetic retinopathy (DR) is thought to be influenced by oxidative stress. Astaxanthin (ASX) is a natural product with antioxidant effect, but it is not clear whether its mechanism of inhibiting the development of DR is related to anti-oxidation.MethodsRats were intraperitoneally injected with streptozotocin (60 mg/kg) to create DR rat models followed by ASX (20 mg/kg) for 45 days. Retinal tissue was examined by Hematoxylin and Eosin staining. By using Enzyme-linked immunosorbent assay (ELISA), 2,7-Dichlorodrhydrofluorescein diace (DCFH-DA) probes, immunohistochemistry and western blot, it was feasible to evaluate the contents of inflammation-related factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and macrophage inhibitory cytokine-1 (MIC-1)), oxidative stress-related indicators (glutathione (GSH), malonic dialdehyde (MDA), glutathione peroxidase (GPx), reactive oxygen species (ROS) and Total antioxidant capacity (T-AOC)), antioxidant enzymes (hemoxgenase-1(HO-1) and Quinone Oxidoreductase 1 (NQO1)), and apoptosis-related proteins (Bcl-2, Bcl2 Associated X Protein (BAX), and cleaved-caspase-3). Additionally, antioxidant proteins downstream of the nuclear factor E2 related factors (Nrf-2) pathway, expression levels of Nrf2/ Kelch-like ECH-associated protein 1(Keap 1) pathway-associated proteins, and nuclear and cytoplasmic levels of Nrf2 were assessed using immunohistochemistry, western blot, or quantitative real-time polymerase chain reaction (qRT-PCR).ResultsASX alleviated retinal tissue damage by increasing overall retina thickness and ganglion cell layer (GCL) cell numbers and exerted the anti-inflammatory, anti-oxidative stress, and anti-apoptosis effects in DR rats. Additionally, ASX could inhibit the expression of Keap1, promote the transport of Nrf2 from cytoplasm to nucleus and facilitate the expressions of HO-1, NQO1, γ-glutamylcysteine synthetase, (γ-GCS) and GPx.ConclusionASX exerted antioxidant effects through Nrf2/keap1 pathway, thereby alleviating apoptosis, inflammation, and oxidative stress in retinal tissues of DR rats.
Keywords:Diabetic retinopathy  Astaxanthin  Nuclear factor erythroid 2-like 2  Kelch-like ECH-associated protein  Antioxidation
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