Effect of Astaxanthin on the Expression of Retinal Oxidative Stress Mediators in Streptozotocin-induced Diabetic Animal Model
Date Issued
2011
Date
2011
Author(s)
Huang, Hsin-Wei
Abstract
1.Background
Diabetic retinopathy, a sight-threatening complication of diabetes, is the major cause of blindness in young adults. Studies have documented that sustained hyperglycemia is the instigating cause of disrupted normal cellular metabolism leading to the development of retinopathy. Diabetes increases oxidative stress, and increased oxidative stress is one of the key regulators in the development of diabetic complications.
Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and antioxidant defense mechanisms.The outer retina is avaseular and receives its oxygen supply from the choroid,which lacks hyperoxia-induced autoregulation. Therefore, photoreceptors are exposed to higher level of tissue oxygen than most other tissue. This phenomenon renders retina more susceptible to oxidative stress.Consequences of chronic oxidative stress include damage to biological macromolecules such as DNA, lipids, proteins, and carbohydrates.
An association between oxidative stress and the development of diabetes complications has been recognized for over 20 years.Increased production of reactive oxygen species has been strongly implicated in the pathogenesis of diabetic retinopathy. Besides, inflammation may also play a central role in the development and progression of diabetic retinopathy.
Astaxanthin (AST), a dietary carotenoid, is often decreasing the formation of products of oxidative damage induced by biological molecules.Astaxanthin is a powerful biological antioxidant occurring naturally in a wide variety of living organisms, and is present in many well-known sea foods such as salmon, trout, red sea-bream, shrimp, lobster and fish eggs. Recent studies have shown that astaxanthin is a powerful biological antioxidant. Due to potent anti-oxidative and anti-inflammatory effects of AST, we hypothesize that AST could reduce the oxidative mediators and increase antioxidant enzyme defense system. Beside, AST may also reduce inflammatory mediators.
2.Purpose
This study is to evaluate the potential protective effects of AST against retinal oxidative damage in streptozotocin(STZ) - induced diabetic rats.
3.Material and Methods
Fifty 6 weeks old female Wistar rats with the body weight about 200-250g were divided into a healthy control group(n=10) and a STZ- induced diabetic group(n=40). These forty rats received intra- peritoneal injection with STZ to induce diabetes and randomly divided into four groups. A group of rats received normal powdered diet or powdered diet supplemented with 0.6 or 3mg/kg AST or 0.5mg/kg lutein.
Eight weeks later, the eyeball of each rat was taken out to obtain fresh retina tissues. We performed immunohistochemistry (IHC), western blot analysis, enzyme-linked immunosorbent assay (ELISA),reverse transcription - polymerase chain reaction (RT-PCR), and electrophoretic mobility shift assays (EMSA) to assess oxidative stress and inflammatory mediators in diabetic retinopathy.
4.Results and discussions
AST could reduce the oxidative mediators (8-hydroxy-2''- deoxyguanosine (8-OHdG), Nitrotyrosine ,and acrolein ) and increase antioxidant enzyme defense system(heme oxygenase, peroxiredoxin, and thioredoxin ). AST also reduce inflammatory mediators (intercellular adhesion molecule (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fractalkine (FKN)) and the activity of transcription factor NF-κB.
5.Conclusions
Astaxanthin could reduce oxidative stress and inflammatory reactions in diabetic retina rat model .The antioxidant and anti-inflammatory effect of Astaxanthin was supposed to be mediated by inhibition of NF-κB activity and reduced the downstream products. Astaxanthin acted as antioxidants by facilitating the activity of antioxidant enzymes to inhibit oxidative stress and reduced the damage to biological macromolecules such as DNA, lipids and proteins. Axtaxanthin seems to be the nutritional supplement for prevention of diabetic retinopathy progression.
Subjects
Astaxanthin
Diabetic retinopathy
Inflammation
Nuclear factor-κB
Oxidative stress
Reactive oxygen species
SDGs
Type
thesis
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