ABSTRACT
15-Lipoxygenase (15-LOX) is one of the key enzymes responsible for the formation of oxidized low-density lipoprotein (ox-LDL), a major causal factor for atherosclerosis. Both enzymatic (15-LOX) and non-enzymatic (Cu(2+)) mechanisms have been proposed for the production of ox-LDL. We have recently reported that cannabidiol-2',6'-dimethyl ether (CBDD) is a selective and potent inhibitor of 15-LOX-catalyzed linoleic acid oxygenation (Takeda et al., Drug Metab. Dispos., 37, 1733-1737 (2009)). In the LDL, linoleic acid is present as cholesteryl linoleate, the major fatty acid esterified to cholesterol, and is susceptible to oxidative modification by 15-LOX or Cu(2+). In this investigation, we examined the efficacy of CBDD on i) 15-LOX-catalyzed oxygenation of cholesteryl linoleate, and ii) ox-LDL formation catalyzed by 15-LOX versus Cu(2+)-mediated non-enzymatic generation of this important mediator. The results obtained demonstrate that CBDD is a potent and selective inhibitor of ox-LDL formation generated by the 15-LOX pathway. These studies establish CBDD as both an important experimental tool for characterizing 15-LOX-mediated ox-LDL formation, and as a potentially useful therapeutic agent for treatment of atherosclerosis.
Subject(s)
Antioxidants/pharmacology , Arachidonate 15-Lipoxygenase/metabolism , Cannabidiol/analogs & derivatives , Cholesterol Esters/metabolism , Cholesterol, LDL/metabolism , Copper/metabolism , Lipoproteins, LDL/biosynthesis , Antioxidants/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Humans , Oxidation-ReductionABSTRACT
Observation of microorganisms by endoscopy has been technically difficult. In this study, we tried to visualize bacteria during endoscopic examination to provide a powerful tool for a diagnosis of gastrointestinal infection. We observed the bacterium Helicobacter pylori, cultured ex vivo, using a novel ultra-high "magnified endoscopy" system ("endocytoscopy" prototype, Olympus Medical Systems). Cultures were prepared from gastric mucus obtained from three gastric ulcer patients. H. pylori in the supernatant of the culture medium were observed directly by endocytoscopy. Staphylococcus aureus and red blood cells were used as controls. H. pylori in the culture medium were observed directly by endocytoscopy, and recorded using a video recorder. Live, moving bacteria can be visualized and recorded ex vivo using this new "endocytoscopy" technology.
