Abstract
BackgroundStatins, HMG-CoA reductase inhibitors, are widely prescribed drugs for dyslipidemias. Recent studies have indicated number of cholesterol independent actions of statins including their beneficial effects on vascular endothelial dysfunction and memory deficits associated with dementia of Alzheimer's type. However the potential of statins in dementia of vascular origin still remains to be explored. Therefore, the present study has been designed to investigate the effect of Atorvastatin & Pitavastatin on vascular endothelial dysfunction associated memory deficits in rats. In this study L-Methionine induced vascular dementia was assessed by Morris water-maze (MWM) test. Biochemical analysis was also performed to unfold possible mechanism of statins mediated modulation of vascular dementia.ResultsL-Methionine produced endothelial dysfunction as reflected by significant decrease in serum nitrite concentration. L-Methionine treated rats performed poorly on MWM indicating impairment of memory as well. These rats also showed a significant rise in brain oxidative stress, acetylcholinesterase (AChE) activity and serum total cholesterol levels. Both Atorvastatin as well as Pitavastatin attenuated L-Methionine induced endothelial dysfunction associated memory deficits. Statins also reversed L-Methionine induced rise in brain oxidative stress, AChE activity and serum cholesterol.ConclusionThe beneficial effects of statins may be attributed to their multiple effects and the study highlights the potential of these drugs in vascular dementia.
Highlights
Statins, HMG-CoA reductase inhibitors, are widely prescribed drugs for dyslipidemias
Effect of Vehicle/Atorvastatin/Pitavastatin/L-Methionine on escape latency time (ELT) and time spent in target quadrant (TSTQ), using Morris water maze (MWM) Vehicle treated (0.5%w/v carboxy methyl cellulose (CMC), 10 ml/kg/p.o.) rats showed a downward trend in their ELT
Young male rats were employed in the present study, as it is reported that aging and consequent variation of estrogen in blood modulates the activity of endothelial nitric oxide synthase, which further affects the function of vascular endothelium and memory [20,21]
Summary
HMG-CoA reductase inhibitors, are widely prescribed drugs for dyslipidemias. Recent studies have indicated number of cholesterol independent actions of statins including their beneficial effects on vascular endothelial dysfunction and memory deficits associated with dementia of Alzheimer's type. The potential of statins in dementia of vascular origin still remains to be explored. The present study has been designed to investigate the effect of Atorvastatin & Pitavastatin on vascular endothelial dysfunction associated memory deficits in rats. In this study L-Methionine induced vascular dementia was assessed by Morris water-maze (MWM) test. Hyperhomocysteinemia (Hhcy), or elevation of plasma total homocysteine, is an important risk factor for cardiovascular disease, stroke and vascular dementia [2,3,4]. Hhcy has been shown to induce endothelial dysfunction by decreasing the bioavailability of NO, and (page number not for citation purposes). The decreased NO level has been demonstrated to contribute to the pathogenesis of dementia [6]
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