title: Administration of sesamol improved blood-brain barrier function in streptozotocin-induced diabetic rats.
abstract: Uncontrolled or poorly controlled blood glucose during diabetes is an important factor in worsened vascular function. While evidence suggests that hyperglycemia-induced oxidative stress plays a prominent role in development of microangiopathy of the retina, kidney, and nerves, the role oxidative stress plays on blood-brain barrier (BBB) function and structure has lagged behind. In this study, a natural antioxidant, sesamol, was administered to streptozotocin (STZ)-induced diabetic rats to examine the role that oxidative stress plays on BBB structure and function. Experiments were conducted at 56 days after STZ injection. Male Sprague-Dawley rats randomly were divided into four treatment groups CON--control; STZ--STZ-induced diabetes; CON + S--control + sesamol; STZ + S--STZ-induced diabetes + sesamol. Functional and structural changes to the BBB were measured by in situ brain perfusion and western blot analysis of changes in tight junction protein expression. Oxidative stress markers were visualized by fluorescent confocal microscopy and assayed by spectrophotometric analysis. Results demonstrated that the increased BBB permeability observed in STZ-induced diabetic rats was attenuated in STZ + S rats to levels observed in CON. Sesamol treatment reduced the negative impact of STZ-induced diabetes on tight junction protein expression in isolated cerebral microvessels. Oxidative stress markers were elevated in STZ as compared to CON. STZ + S displayed an improved antioxidant capacity which led to a reduced expression of superoxide and peroxynitrite and reduced lipid peroxidation. In conclusion, this study showed that sesamol treatment enhanced antioxidant capacity of the diabetic brain and led to decreased perturbation of hyperglycemia-induced changes in BBB structure and function.
authors: Department of Basic Pharmaceutical Sciences, West Virginia University, P.O. Box 9530, Morgantown, WV 26506, USA.
authors: R L
authors: RL
authors: VanGilder
authors: K A
authors: KA
authors: Kelly
authors: M D
authors: MD
authors: Chua
authors: R L
authors: RL
authors: Ptachcinski
authors: Jason D
authors: JD
authors: Huber
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D062507:Claudin-5; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D004996:Ethidium / Q000031:analogs & derivatives; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry / Q000379:methods; D013311:Streptozocin; D062826:Zonula Occludens-1 Protein
chemical_list: D000975:Antioxidants; D052117:Benzodioxoles; D001786:Blood Glucose; D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D010636:Phenols; D010750:Phosphoproteins; D012333:RNA, Messenger; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C067883:dihydroethidium; D030421:Peroxynitrous Acid; D013311:Streptozocin; C025583:sesamol; D002374:Catalase; D004996:Ethidium