The hydrogen sulfide releasing compounds ATB-346 and diallyl trisulfide attenuate streptozotocin-induced cognitive impairment, neuroinflammation, and oxidative stress in rats: involvement of asymmetric dimethylarginine

• Published in: Canadian journal of physiology and pharmacology Vol. 94; no. 7; pp. 699 - 708
• Main Authors: Mostafa, Dalia K, El Azhary, Nesrine M, Nasra, Rasha A
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.07.2016; Canadian Science Publishing NRC Research Press
• Subjects: Allyl Compounds - pharmacology; Allyl Compounds - therapeutic use; Alzheimer disease; Amino acids; Animals; Arginine - analogs & derivatives; Arginine - metabolism; ATB-34; ATB-346; Care and treatment; Chemical compounds; Cognition & reasoning; Cognition disorders; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - prevention & control; diallyl trisulfide; et trisulfure de di-allyle; Health aspects; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - prevention & control; Inflammation Mediators - metabolism; maladie d’Alzheimer; Male; Maze Learning - drug effects; Maze Learning - physiology; Naproxen - analogs & derivatives; Naproxen - pharmacology; Naproxen - therapeutic use; Nervous system diseases; neuro-inflammation; neuroinflammation; Organosulfur compounds; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Wistar; Rodents; Streptozocin - toxicity; stress oxydant; Sulfides - pharmacology; Sulfides - therapeutic use; sulfure d’hydrogène; neuro-inflammation; et trisulfure de di-allyle; diallyl trisulfide; ATB-346; hydrogen sulfide; Alzheimer disease; maladie d’Alzheimer; neuroinflammation; ATB-34; sulfure d’hydrogène; oxidative stress; stress oxydant
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2015-0316

Hydrogen sulfide (H 2 S) has attracted interest as a gaseous mediator involved in diverse processes in the nervous system, particularly with respect to learning and memory. However, its therapeutic potential in Alzheimer disease (AD) is not fully explored. Therefore, the effects of H 2 S-releasing compounds against AD-like behavioural and biochemical abnormalities were investigated. Memory deficit was induced by intracerberoventicular injection of streptozotocin (STZ, 3 mg·kg −1 ). Animals were randomly assigned into 5 groups (12 rats each): normal control, STZ treated, and 3 drug-treated groups receiving naproxen, H 2 S-releasing naproxen (ATB-346), and diallyl trisulfide in 20, 32, 40 mg·kg −1 ·day −1 , respectively. Memory function was assessed by passive avoidance and T-maze tasks. After 21 days, hippocampal IL-6, malondialdehyde, reduced glutathione (GSH), asymmetric dimethylarginine (ADMA), and acetylcholinestrase activity were determined. ATB-346 and diallyl trisulfide ameliorated behavioural performance and reduced malondialdehyde, ADMA, and acetylcholinestrase activity while increasing GSH. This study demonstrates the beneficial effects of H 2 S release in STZ-induced memory impairment by modulation of neuroinflammation, oxidative stress, and cholinergic function. It also delineates the implication of ADMA to the cognitive impairment induced by STZ. These findings draw the attention to H 2 S-releasing compounds as new candidates for treating neurodegenerative disorders that have prominent oxidative and inflammatory components such as AD.