Tadalafil ameliorates memory deficits, oxidative stress, endothelial dysfunction and neuropathological changes in rat model of hyperhomocysteinemia induced vascular dementia.
Int J Neurosci
; 132(4): 384-396, 2022 Apr.
Article
in En
| MEDLINE
| ID: mdl-32859137
ABSTRACT
AIM:
The present study investigates the potential of Tadalafil, a phosphodiesterase-5 inhibitor, in a rat model of hyperhomocysteinemia induced vascular dementia.METHODS:
Hyperhomocysteinemia induced vascular dementia in Wistar rats was produced by administering l-Methionine (1.7 g/kg/day; p.o.×8 weeks). Learning and memory was assessed by employing Morris water maze (MWM) test. Endothelial dysfunction was assessed through acetylcholine-induced endothelial-dependent vasorelaxation and serum nitrite levels. Various other biochemical and histopathological estimations were also performed.RESULTS:
l-Methionine produced significant impairment in acetylcholine-induced endothelium-dependent vasorelaxation and a decrease in serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on Morris water maze, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by an increase in brain thiobarbituric acid reactive species and a decrease in reduced glutathione levels). Increase in brain acetylcholinesterase activity; brain myeloperoxidase activity and brain neutrophil infiltration (a marker of inflammation) were also observed. Tadalafil (5 and 10 mg/kg, p.o.)/Donepezil (0.5 mg/kg, i.p., serving as standard) treatment ameliorated l-Methionine induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner.CONCLUSIONS:
It may be concluded that tadalafil has shown efficacy in the rat model of l-Methionine induced vascular dementia and that phosphodiesterase-5 can be considered as an important therapeutic target for the treatment of vascular dementia.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dementia, Vascular
/
Hyperhomocysteinemia
/
Tadalafil
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Int J Neurosci
Year:
2022
Document type:
Article
Affiliation country:
India