A friend has been sending me a great deal of information about Nrf2.
I'm in the process of reading through published articles on this.
SLC
https://en.wikipedia.org/wiki/NFE2L2
Dimethyl fumarate, marketed as Tecfidera by Biogen Idec, was approved by the Food and Drug Administration in March 2013 following the conclusion of a Phase III clinical trial which demonstrated that the drug reduced relapse rates and increased time to progression of disability in people with multiple sclerosis.[6] The mechanism by which it exerts its therapeutic effect is unknown. Dimethyl fumarate (and its metabolite, monomethyl fumarate) activates the NRF2 pathway and has been identified as a nicotinic acid receptor agonist in vitro.[37] The label includes warnings about the risk of anaphylaxis and angioedema, progressive multifocal leukoencephalopathy (PML), lymphopenia, and liver damage; other adverse effects include flushing and gastrointestinal events, such as diarrhea, nausea, and upper abdominal pain.[37]
The dithiolethiones are a class of organosulfur compounds, of which oltipraz, an NRF2 inducer, is the best studied.[38] Oltipraz inhibits cancer formation in rodent organs, including the bladder, blood, colon, kidney, liver, lung, pancreas, stomach, and trachea, skin, and mammary tissue.[39] However, clinical trials of oltipraz have not demonstrated efficacy and have shown significant side effects, including neurotoxicity and gastrointestinal toxicity.[39] Oltipraz also generates superoxide radical, which can be toxic.[40]
The following study although it does not mention Protandim nrf2 by name does discuss macular degeneration and dietary polyphenols.
Genetic activation of NRF2 may promote the development of de novo cancerous tumors[41][42] as well as the development of atherosclerosis by raising plasma cholesterol levels and cholesterol content in the liver.[43] It has been suggested that the latter effect may overshadow the potential benefits of antioxidant induction afforded by NRF2 activation.[43][44]
Oxid Med Cell Longev. 2012; 2012: 132931.
Phytochemical Activation of Nrf2 Protects Human Coronary Artery Endothelial Cells against an Oxidative Challenge
Abstract
Activation of NF-E2-related factor 2 (Nrf2) is a potential therapeutic intervention against endothelial cell oxidative stress and associated vascular disease. We hypothesized that treatment with the phytochemicals in the patented dietary supplement Protandim would induce Nrf2 nuclear localization and phase II antioxidant enzyme protein in human coronary artery endothelial cells (HCAECs), protecting against an oxidant challenge in an Nrf2- dependent manner. Protandim treatment induced Nrf2 nuclear localization, and HO-1 (778% of control ± 82.25 P < 0.01), SOD1 (125.9% of control ± 6.05 P < 0.01), NQO1 (126% of control ± 6.5 P < 0.01), and GR (119.5% of control ± 7.00 P < 0.05) protein expression in HCAEC. Treatment of HCAEC with H2O2 induced apoptosis in 34% of cells while pretreatment with Protandim resulted in only 6% apoptotic cells (P < 0.01). Nrf2 silencing significantly decreased the Protandim-induced increase in HO-1 protein (P < 0.01). Nrf2 silencing also significantly decreased the protection afforded by Protandim against H2O2- induced apoptosis (P < 0.01 compared to no RNA, and P < 0.05 compared to control RNA). These results show that Protandim induces Nrf2 nuclear localization and antioxidant enzyme expression, and protection of HCAEC from an oxidative challenge is Nrf2 dependent..
Abstract
Activation of NF-E2-related factor 2 (Nrf2) is a potential therapeutic intervention against endothelial cell oxidative stress and associated vascular disease. We hypothesized that treatment with the phytochemicals in the patented dietary supplement Protandim would induce Nrf2 nuclear localization and phase II antioxidant enzyme protein in human coronary artery endothelial cells (HCAECs), protecting against an oxidant challenge in an Nrf2- dependent manner. Protandim treatment induced Nrf2 nuclear localization, and HO-1 (778% of control ± 82.25 P < 0.01), SOD1 (125.9% of control ± 6.05 P < 0.01), NQO1 (126% of control ± 6.5 P < 0.01), and GR (119.5% of control ± 7.00 P < 0.05) protein expression in HCAEC. Treatment of HCAEC with H2O2 induced apoptosis in 34% of cells while pretreatment with Protandim resulted in only 6% apoptotic cells (P < 0.01). Nrf2 silencing significantly decreased the Protandim-induced increase in HO-1 protein (P < 0.01). Nrf2 silencing also significantly decreased the protection afforded by Protandim against H2O2- induced apoptosis (P < 0.01 compared to no RNA, and P
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