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.