L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration

Dulull, Nabeela K.; Dias, Daniel A.; Thrimawithana, Thilini; Kwa, Faith A.A.

doi:10.2174/1874467211666180125163009

Cited by 18 publications

(16 citation statements)

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“…Sulforaphane protects mouse retina from ultraviolet light by upregulating the expression of thioredoxin, an antioxidant protein whose expression is driven by Nrf2. Moreover, sulforaphane exerted protection of ARPE-19 cell line exposed to 400 μM H 2 O 2 by up-regulating the translation of thioredoxin and Nrf2 ( Tanito et al, 2005 ) and has been suggested to promote regeneration of retinal cells ( Dulull et al, 2018 ). Recently the protective effect of sulforaphane on RPE cells was correlated with preventing mitochondrial fission independently of Nrf2 activation ( O’Mealey et al, 2017 ).…”

Section: Nrf2 Activating Compounds In Amd Therapymentioning

confidence: 99%

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

2018

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Age-related macular degeneration is one of the leading causes of vision loss in the elderly. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. All these risk factors are linked to the induction of oxidative stress. In young subjects retinal pigment epithelial cells mitigate reactive oxygen generation by the elimination of dysfunctional mitochondria, via mitophagy, and by increasing antioxidant defenses via Nrf2 activation. The high amount of UV light absorbed by the retina, together with cigarette smoking, cooperate with the aging process to increase the amount of reactive oxygen species generated by retinal pigment epithelium where oxidative stress arises. Moreover, in the elderly both the mitophagic process and Nrf2 activation are impaired thus causing retinal cell death. This review will focus on the impact of oxidative stress on the pathogenesis of age-related macular degeneration and analyze the natural and synthetic Nrf2-activating compounds that have been tested as potential therapeutic agents for the disease.

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Section: Nrf2 Activating Compounds In Amd Therapymentioning

confidence: 99%

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

2018

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“…Spatial learning and memory dysfunction [135] Chemotherapy-induced neuropathic pain [136] Protection of granulosa cells against oxidative stress [137] Cadmium-mediated carcinogenesis [138] Oxidative stress in cultured adult cardiomyocytes [139] Protective effects of glucosinolate hydrolysis products in neurodegenerative diseases [140] Clearance of Amyloid-β and Tau protein in a mouse model of AD [141] Experimental diabetic peripheral neuropathy [142] Joint inflammation in a murine adjuvant-induced mono-arthritis [143] Protection against cognitive impairment in AD-like lesions in diabetes [144] Anti-inflammatory effect of SFN on human THP-1 macrophages in a murine AD model [145] Inhibition of oxidative stress/inflammation improves cardiac function in a Rabbit Model of Chronic Heart Failure [146] Inhibition of class IIa histone deacetylase activity [147] Apoptosis via microtubule disruption in cancer [148] Inhibition of LPS-Induced Inflammation/cytotoxicity/oxidative microglial stress [149] Down-regulation of MAPK/NF-κB signaling in LPS-activated BV-2 microglia [150] Inhibition of oxidative stress in an in vitro model of age-related macular degeneration [151] Modification of Histone H3, unpacking of chromatin, to prime defence [128] Modulation of oxidative stress and inflammation in rats with toxic hepatitis [152] Modulation of oxidative damage in lead exposed rat hippocampus [153] Table 5. Cont.…”

Section: Medical Conditions Treated With Sulphoraphanementioning

confidence: 99%

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

Melrose

2019

Biomedicines

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This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and antimicrobial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant “priority pathogens” and also act as anti-cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

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“…The culture media was further supplemented with 10% foetal calf serum (FCS; Sigma Aldrich, USA) and 1% penicillin-streptomycin 10,000 U/ml (Life Technologies, USA). The ARPE-19 cells were sustained at 37 ° C in an atmosphere of 95% air and 5% CO 2 , and phenotypic characteristics of these cells were validated in our previous publication 24 .…”

Section: Methodsmentioning

confidence: 90%

“…In 2018, our laboratory reported the ability of LSF at micro molar concentrations (3µM and 5µM) to protect human retinal pigment epithelium from cell death and promoted the regeneration of these cells under oxidative stress conditions 24 . This preliminary study involving gas chromatography mass spectrometry (GC-MS) analytical methods revealed that LSF treatment induced changes in the levels of FAs, such as nonanoic acid and 9,12,15- (Z-Z-Z)-Octodectrienoic acid, and upregulated the levels of GSTM1 gene expression 24 . However, many of these significant changes were observed with the 5µM LSF treatment.…”

Section: Introductionmentioning

confidence: 99%

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

et al. 2020

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Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients’ quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection. Methods: The in vitro oxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry. Results: Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolamine lipids. Conclusions: We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD.

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L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration

Abstract: This study supports the use of L-Sulforaphane to promote regeneration of retinal cells under oxidative stress conditions.

Cited by 18 publications

References 0 publications

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

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