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.

• Authors: Pankaj Bhatia, Nirmal Singh
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 132 Issue 4 Pg. 384-396 (Apr 2022) ISSN: 1563-5279 [Electronic] England
• PMID: 32859137 (Publication Type: Journal Article)

Chemical References

• Nitrites
• Phosphodiesterase 5 Inhibitors
• Tadalafil
• Methionine
• Acetylcholinesterase
• Cyclic Nucleotide Phosphodiesterases, Type 5
• Acetylcholine

Topics

• Acetylcholine
• Acetylcholinesterase (metabolism)
• Animals
• Brain (metabolism)
• Cyclic Nucleotide Phosphodiesterases, Type 5
• Dementia, Vascular (drug therapy, etiology)
• Hyperhomocysteinemia (chemically induced, complications, drug therapy)
• Maze Learning
• Memory Disorders (chemically induced, drug therapy)
• Methionine
• Nitrites (blood)
• Oxidative Stress
• Phosphodiesterase 5 Inhibitors
• Rats
• Rats, Wistar
• Tadalafil (therapeutic use)