Pitavastatin and 4-Hydroxy-3-Methoxyacetophenone (HMAP) Reduce Cognitive Dysfunction in Vascular Dementia During Experimental Diabetes

Abstract

Diabetes has been found to increase the probability of vascular dementia in humans. We have investigated the effect of 4'-hydroxy-3'-methoxyacetophenone (HMAP), a NADPH oxidase inhibitor and Pitavastatin, HMG Co-A reductase inhibitor, on Streptozotocin (STZ) diabetes induced vascular dementia in rats. Donepezil served as a positive control. The rats were administered with single dose of STZ for the induction of diabetes. Drug treatment was started after one month of STZ administration and treatment was continued till the end of the study (i.e. 56th day). On 52nd day onwards, the animals were exposed to Morris water-maze (MWM) for testing learning & memory. Serum glucose, bodyweight, vascular endothelial function, serum nitrite / nitrate levels, aortic & brain oxidative stress levels and brain acetylcholinesterase activity were also tested. STZ treated animals performed poorly on MWM hence reflecting impairment of learning & memory. Further STZ treatment also produced a reduction in body weight, impairment of vascular endothelial function, decrease in serum nitrite / nitrate levels, along with increase in serum glucose, aortic & brain oxidative stress levels and brain acetylcholinesterase activity. Treatment of HMAP, Pitavastatin and Donepezil significantly reversed diabetes induced learning and memory, endothelial dysfunction, and changes in various biochemical levels. It may be concluded that STZ induces vascular dementia. 4'hydroxy-3'-methoxy acetophenone and Pitavastatin may be considered as potential pharmacological agents for the management of diabetes induced vascular dementia.

Attenuating effect of lisinopril and telmisartan in intracerebroventricular streptozotocin induced experimental dementia of Alzheimer’s disease type: possible involvement of PPAR-γ agonistic property

“…Whole brain AChE activity was measured spectrophotometerically (DU 640B spectrophotometer, Beckman Coulter Inc., California, USA) at 420 nm by the method of Ellman et al 30,31 with slight modification. 16,29 Briefly, this was measured on the basis of the formation of yellow color due to the reaction of thiocholine with dithiobisnitrobenzoate ions. The rate of formation of thiocholine from acetylthiocholine iodide in the presence of brain cholinesterase was measured using a spectrophotometer.…”

“…The quantitative measurement of TBARS, an index of lipid peroxidation in brain was performed according to the method of Ohkawa et al 16,29,34 Thus, 0.2 ml of supernatant of homogenate was pipetted out in a test tube, followed by addition of 0.2 ml of 8.1% sodium dodecyl sulphate, 1.5 ml of 30% acetic acid (pH 3.5), 1.5 ml of 0.8% of thiobarbituric acid and the volume was made up to 4 ml with distilled water. The test tubes were incubated for 1 hr at 95°C, then cooled and 1 ml of distilled water added followed by addition of 5 ml of n-butanol-pyridine mixture (15:1 v/v).…”

Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats

“…in 0.1 M citrate buffer (pH 4.5) to induce experimental diabetes mellitus and associated dementia (Rakieten et al 1963;Brosky and Logothetopoulos 1969;Sharma and Singh 2010). Serum glucose levels of the animals were measured every week.…”

“…Furthermore, it has been observed that there is a significant association of impaired glucose metabolism with incidence of VaD (Curb et al 1999) as well as dementia of Alzheimer's disease (Arvanitakis et al 2004;Xu et al 2007). Very recently, in a study from our own laboratory, we have demonstrated induction of VaD associated with streptozotocin (STZ) diabetes in rats (Sharma and Singh 2010).…”

Bamboo leaf extract improves spatial learning ability in a rat model with senile dementia

“…Senile dementia (SD) causes long term deficit in memory and cognition that is severe enough to affect a person's daily functioning (Sharma and Singh, 2010). It is reported that in China the number of people with dementia is 6-7 million with an incidence of 5%-7% of people over 65 years of age (Song and Wang, 2010).…”