Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.
The study was designed to investigate the efficacy of bosentan a dual endothelin (ETA and ETB) receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia. Diabetes was induced in rats by administration of a single dose (50mg/kg, i.p.) of streptozotocin (STZ). Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing spatial learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and brain acetylcholinesterase activity were also tested. STZ treatment resulted in significant development of cognitive and vascular endothelial deficits, manifested in the terms of endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate levels along with increase in serum glucose, brain acetylcholinesterase activity, TBARS, and decreased GSH levels. Treatment of bosentan attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters. It may be concluded that bosentan has shown efficacy in STZ induced cognitive and vascular endothelial deficits. Thus, endothelin receptors can be considered as a potential pharmacological target for the management of experimental diabetes induced vascular endothelial dysfunction and associated dementia.
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala 147002, Punjab, India. Electronic address: gpreet_toor@ymail.com.
Gurpreet
G
Singh
Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Bypass Road, Partapur, Meerut 250103, Uttar Pradesh, India. Electronic address: drbhupeshresearch@gmail.com.
Bhupesh
B
Sharma
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala 147002, Punjab, India. Electronic address: amteshwarjaggi@yahoo.co.in.
Amteshwar Singh
AS
Jaggi
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala 147002, Punjab, India. Electronic address: nirmalresearch@gmail.com.
Nirmal
N
Singh
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000077300:Bosentan; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003704:Dementia / Q000150:complications* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology*; D065131:Endothelin B Receptor Antagonists / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013449:Sulfonamides / Q000494:pharmacology*
D001786:Blood Glucose; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D009566:Nitrates; D009573:Nitrites; D013449:Sulfonamides; D013311:Streptozocin; D000110:Acetylcholinesterase; D005978:Glutathione; D000077300:Bosentan
Diabetes; Moris water maze; Nitrite/nitrate; Oxidative stress; Streptozotocin; Vascular dementia