title: Comparison of protective effects of aspirin, D-penicillamine and vitamin E against high glucose-mediated toxicity in cultured endothelial cells.
abstract: This study compared the protective effects of three different anti-glycation compounds, aspirin, D-penicillamine and vitamin E, against high glucose and advanced glycation endproduct (AGE) mediated toxicity in cultured bovine aortic endothelial cells using two approaches. Their proliferation was assessed in culture in different concentrations of glucose (5.5-100 mmol/l) with and without these inhibitors. A monolayer of cultured endothelial cells was wounded and recovery at the wound site was measured following exposure to different concentrations of glucose with and without inhibitors. The ability of these compounds to protect cultured endothelial cells following exposure to bovine serum albumin-derived advanced glycation endproducts (BSA-AGE) was also studied. Addition of glucose to cultured endothelial cells inhibited their proliferation in a dose dependent manner. All three compounds protected against the anti-proliferative effects of high glucose, with vitamin E being the most effective. The migration of cultured endothelial cells following wounding was inhibited by increasing concentrations of glucose but was maintained in the presence of all three anti-glycation compounds with vitamin E, again giving the greatest protection. Vitamin E was also the most effective at protecting against the anti-proliferative effects of BSA-AGE. D-penicillamine was not as effective as vitamin E whereas aspirin offered no significant protection against AGE-induced cellular toxicity. Our studies suggest that compounds, such as vitamin E, with combined antiglycation and antioxidant properties offer maximum therapeutic potential in protection against high glucose and AGE-mediated cellular toxicity.
authors.affiliation: School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Oxford Road, Manchester M1 5GD, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Slevin
authors.forename: Yasotha
authors.initials: Y
authors.lastname: Duraisamy
authors.forename: John
authors.initials: J
authors.lastname: Gaffney
authors.forename: Christopher
authors.initials: C
authors.lastname: A Smith
authors.forename: Nessar
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology / Q000633:toxicity*; D010396:Penicillamine / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D014810:Vitamin E; D012710:Serum Albumin, Bovine; D010396:Penicillamine; D005947:Glucose; D001241:Aspirin