title: Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats.
abstract: The study has been designed to investigate the effect of demethylasterroquinone B1 (DAQ B1), an activator of Akt, in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction. Streptozotocin (55 mg kg(-1), i.v.) and methionine (1.7% w/w, p.o., 4 weeks) were administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum homocysteine >10 microM), respectively. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta and serum concentration of nitrite/nitrate. The expression of messenger RNA for p22phox and eNOS was assessed by reverse transcription-polymerase chain reaction. Serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion were estimated to assess oxidative stress. DAQ B1 (5 mg kg(-1), p.o.) or atorvastatin (30 mg kg(-1), p.o.) in diabetic and hyperhomocysteinemic rats significantly reduced serum glucose and homocysteine concentration. DAQ B1 or atorvastatin markedly improved acetylcholine-induced endothelium-dependent relaxation, vascular endothelial lining, serum nitrite/nitrate concentration and serum TBARS in diabetic and hyperhomocysteinemic rats. However, this ameliorative effect of DAQ B1 has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor of eNOS. Therefore, it may be concluded that DAQ B1-induced activation of Akt may activate eNOS and consequently reduce oxidative stress to improve vascular endothelial dysfunction.
authors.affiliation: Department of Pharmaceutical Sciences & Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002,
authors.forename: Dhvanit I
authors.initials: DI
authors.lastname: Shah
authors.forename: Manjeet
authors.initials: M
authors.lastname: Singh
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology* / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D009566:Nitrates; D009573:Nitrites; D011809:Quinones; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; D013481:Superoxides; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine