Ameliorative role of Atorvastatin and Pitavastatin in L-Methionine induced vascular dementia in rats.
BACKGROUND
Statins, 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.


RESULTS
L-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.


CONCLUSIONS
The beneficial effects of statins may be attributed to their multiple effects and the study highlights the potential of these drugs in vascular dementia.
Koladiya
Rajeshkumar U
RU
Department of Pharmaceutical Sciences & Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, India. rajpatel_20982@yahoo.co.in
Jaggi
Amteshwar S
AS
Singh
Nirmal
N
Sharma
Bhupesh K
BK
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D000069059:Atorvastatin; D015140:Dementia, Vascular / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008715:Methionine; D011758:Pyrroles / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D000069059:Atorvastatin; D008715:Methionine; C108475:pitavastatin