title: Efficacy of Cilostazol a selective phosphodiesterase-3 inhibitor in rat model of Streptozotocin diabetes induced vascular dementia.
abstract: The present study has been designed to investigate the potential of Cilostazol a phosphodiesterase-3 (PDE-3) inhibitor in diabetes-induced vascular dementia (Vad) employing Wistar rats. A single dose of Streptozotocin (STZ) was used for the induction of diabetes and subsequent Vad in rats. Memory and learning abilities of rats were evaluated with Morris water maze (MWM) test. Serum glucose, body weight, vascular endothelial function, serum nitrite/nitrate levels, brain oxidative stress levels (viz. brain thiobarbituric acid reactive species and reduced glutathione levels), inflammatory markers (viz. brain myeloperoxidase activity and neutrophil infiltration in the brain hippocampal area) and brain acetylcholinesterase activity were also tested. Donepezil was used as positive control. Streptozotocin treated animals showed poor performance on MWM indicating impairment of learning and memory abilities with a significant reduction in body weight, vascular endothelial function, serum nitrite/nitrate levels, along with an increase in serum glucose, brain oxidative stress levels, inflammatory changes and brain acetylcholinesterase activity. Treatment with selective PDE-3 inhibitor, Cilostazol significantly attenuated, diabetes-induced impairment of learning and memory; endothelial dysfunction, and changes in various biochemical parameters. It is concluded that selective PDE-3 inhibitor, Cilostazol may be considered as the potential pharmacological agent for the management of diabetes-induced vascular dementia.
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
authors.forename: Amteshwar S
authors.initials: AS
authors.lastname: Jaggi
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India. Electronic address: nirmal_puru@rediffmail.com.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D000077407:Cilostazol; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol
keywords: Diabetes; Morris water maze; Nitrite/nitrate; Oxidative stress; Streptozotocin; Vascular dementia