Beneficial Effect of Protein Tyrosine Phosphatase Inhibitor and Phytoestrogen in Dyslipidemia-Induced Vascular Dementia in Ovariectomized Rats.
BACKGROUND
Estrogen deficiency and increase in protein tyrosine phosphatase (PTPase) activity may be a key mechanism in postmenopausal dyslipidemia-induced vascular dysfunction and dementia. Thus, the present study has been designed to investigate the effect of biochanin A (BCA, a phytoestrogen) and sodium orthovanadate (SOV), an inhibitor of PTPase in dyslipidemia-induced vascular dementia in ovariectomized rats.


METHODS
Female Wistar rats were ovariectomized and fed on high fat diet for 4 weeks to produce dyslipidemia. Dyslipidemia was assessed by estimation of serum lipid levels including total cholesterol, triglyceride, HDL, and LDL levels. Dementia was assessed in terms of increase in brain acetylcholinesterase (AChE) activity and attenuation of learning ability (escape latency time) and memory retention (time spent in target quadrant) using Morris water maze. Vascular dysfunction was assessed in terms of attenuation of acetylcholine-induced endothelium-dependent relaxation (isolated carotid ring preparation), mRNA expression of endothelial nitric oxide synthase, and increase in serum thiobarbituric acid reactive species, superoxide anion level. Neurodegeneration was assessed in hippocampus by hematoxylin and eosin staining. BCA (2.5 and 5 mg/kg) and SOV (5 and 10 mg/kg) were administered alone and in low-dose combination to ovariectomized dyslipidemic rats.


RESULTS
BCA (2.5 and 5 mg/kg), SOV (5 and 10 mg/kg), and donepezil (1 mg/kg) significantly improves vascular function, and learning and memory ability and decreases the neuronal cell death, oxidative stress, and AChE in ovariectomized dyslipidemic rats.


CONCLUSIONS
Thus, it may be concluded that BCA and SOV attenuate vascular dysfunction and dementia in dyslipidemic ovariectomized rats.
Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India.
Aditi
A
Verma
Department of Pharmacology, I.S.F College of Pharmacy, Moga, Punjab, India. Electronic address: ssm.research@gmail.com.
Saurabh
S
Sharma
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology; D000077265:Donepezil; D050171:Dyslipidemias / Q000150:complications; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000627:therapeutic use*; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D011939:Mental Recall / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D048789:Phytoestrogens / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D007189:Indans; D008055:Lipids; D048789:Phytoestrogens; D010880:Piperidines; D014638:Vanadates; D000077265:Donepezil; D019833:Genistein; D052250:Nitric Oxide Synthase Type III; D000110:Acetylcholinesterase; C004541:biochanin A
Vascular dementia; dyslipidemia; ovariectomy; vascular endothelium dysfunction