title: Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway.
abstract: BACKGROUND
  Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway.
  
  
  METHODS
  Male Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot.
  
  
  RESULTS
  HF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG.
  
  
  CONCLUSIONS
  GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Zuo
authors.forename: Chong
authors.initials: C
authors.lastname: Tian
authors.forename: Nana
authors.initials: N
authors.lastname: Zhao
authors.forename: Weiye
authors.initials: W
authors.lastname: Ren
authors.forename: Yi
authors.initials: Y
authors.lastname: Meng
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shibin
authors.initials: S
authors.lastname: Ding
authors.forename: Chenjiang
authors.initials: C
authors.lastname: Ying
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou 325035, PR China. yexiaolei302@163.com.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Ye
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry*
chemical_list: D009861:Onium Compounds; D059808:Polyphenols; D017382:Reactive Oxygen Species; D013662:Tea; C007517:diphenyleneiodonium; D009247:NADH, NADPH Oxidoreductases; C583073:NCF2 protein, rat; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D005947:Glucose