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.
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Authors | Dhvanit I Shah, Manjeet Singh |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 295
Issue 1-2
Pg. 65-74
(Jan 2007)
ISSN: 0300-8177 [Print] Netherlands |
PMID | 16841179
(Publication Type: Journal Article)
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Chemical References |
- Blood Glucose
- Nitrates
- Nitrites
- Quinones
- RNA, Messenger
- Thiobarbituric Acid Reactive Substances
- Homocysteine
- Superoxides
- Nitric Oxide Synthase Type III
- NADPH Oxidases
- Cyba protein, rat
- Proto-Oncogene Proteins c-akt
- Acetylcholine
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Topics |
- Acetylcholine
(pharmacology)
- Animals
- Aorta
(drug effects, enzymology, ultrastructure)
- Blood Glucose
(metabolism)
- Diabetes Mellitus, Experimental
(chemically induced, enzymology, physiopathology)
- Endothelium, Vascular
(enzymology, physiopathology, ultrastructure)
- Gene Expression Regulation, Enzymologic
(drug effects)
- Homocysteine
(blood)
- Hyperhomocysteinemia
(chemically induced, enzymology, physiopathology)
- Male
- NADPH Oxidases
(genetics, metabolism)
- Nitrates
(blood)
- Nitric Oxide Synthase Type III
(genetics, metabolism)
- Nitrites
(blood)
- Proto-Oncogene Proteins c-akt
(agonists, metabolism)
- Quinones
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Wistar
- Superoxides
(metabolism)
- Thiobarbituric Acid Reactive Substances
(analysis)
- Vasodilation
(drug effects)
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