Tadalafil ameliorates memory deficits, oxidative stress, endothelial dysfunction and neuropathological changes in rat model of hyperhomocysteinemia induced vascular dementia

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.

Keywords:

• Phosphodiesterase-5
• Tadalafil
• hyperhomocysteinemia
• oxidative stress
• memory
• vascular dementia

Acknowledgments

The authors are grateful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, for providing technical facilities for carrying out research.

Disclosure statement

No potential conflict of interest was reported by the author(s).