Oxidative stress, inflammation, and diabetic vasculopathies: the role of alpha tocopherol therapy.
The diabetic state confers an increased propensity to accelerated atherogenesis. In addition to the established risk factors, there is evidence for increased oxidative stress and inflammation in diabetes. Increased oxidative stress is manifested by increased lipid peroxidation (e.g. increased F2-isoprostanes) and increased DNA damage. Evidence for increased inflammation includes increased monocyte superoxide and pro-inflammatory cytokine release (IL-1, IL-6, and TNF-alpha), increased monocyte adhesion to endothelium and increased levels of plasma C-reactive protein, the prototypic marker of inflammation. Most importantly, alpha tocopherol therapy, especially at high doses, clearly shows a benefit with regards to LDL oxidation, isoprostanes and a decrease in inflammatory markers such as C-reactive protein, pro-inflammatory cytokines and PAI-1 levels. Thus, it appears that, in diabetes, alpha tocopherol therapy could emerge as an additional therapeutic modality.
Jialal
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I
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, UC Davis Medical Center, Sacramento, CA, USA. ishwarlal.jialal@ucdmc.ucdavis.edu
Devaraj
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Venugopal
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SK
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D048909:Diabetes Complications; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D024502:alpha-Tocopherol / Q000627:therapeutic use*
D007375:Interleukin-1; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D002097:C-Reactive Protein; D024502:alpha-Tocopherol