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Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats

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Abstract

The study has been designed to investigate the effect of demethylasterroquinone B1 (DAQ B1), an activator of Akt, in diabetes mellitus (DM) and hyperhomocyteinemia (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 µM), 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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  1. Department of Pharmaceutical Sciences & Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002, Punjab, India

    Dhvanit I. Shah & Manjeet Singh

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Shah, D.I., Singh, M. Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats. Mol Cell Biochem 295, 65–74 (2007). https://doi.org/10.1007/s11010-006-9273-9

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