title: Memory recuperative potential of rifampicin in aluminum chloride-induced dementia: role of pregnane X receptors.
abstract: The present study has been designed to investigate the potential of rifampicin [Pregnane X receptors (PXR) agonist] in experimental dementia. Aluminum chloride (AlCl3) [100mg/kg, p.o. for 42days] was administered to Wistar rats (n=6) to induce dementia. Morris water maze (MWM) test was used to assess learning and memory and rota rod test was used to assess locomotor activity of the animals. A battery of biochemical tests and histopathological evaluation using hematoxylin and eosin (H&E) and Congo Red stains were performed at the end of the study. AlCl3-treated rats demonstrated impaired cognition and locomotor activity on MWM apparatus and rota rod test, respectively. These animals exhibited a significant rise in acetylcholinesterase (AChE) activity (138±3.6), thiobarbituric acid reactive species (TBARS) level (15±1.6), nitrite (56±2.4) level and myeloperoxidase (MPO) activity (4.1±0.9) along with decline in reduced glutathione (GSH) level (22±1.3) in comparison to the control group (p<0.05). Further the H&E and Congo Red-stained cerebral cortex sections of AlCl3-treated rats indicated severe neutrophilic infiltration and amyloid deposition. Rifampicin-treated AlCl3-rats exhibited significant attenuation in memory deficits, biochemical parameters like AChE activity (33±1.4), TBARS level (4.1±1.0), nitrite level (64±2.6), MPO activity (3.6±1.0) and GSH level (53±2.4) along with improved histopathological alterations and locomotor activity when compared with AlCl3-treated rats (p<0.05). Combined administration of ketoconazole (a PXR antagonist) and rifampicin to AlCl3-treated animals reversed the rifampicin-induced protective effects. Therefore the results obtained from the study indicate a defensive role of rifampicin in memory dysfunction which may probably be due to its anti-cholinesterase, anti-oxidative, anti-inflammatory and amyloid lowering effects. Moreover the study speculates the potential of PXR in the pathophysiology of dementia which is subject to further evaluation.
authors.affiliation: Pharmacology Division, Chandigarh College of Pharmacy, Landran, Mohali 140307, Punjab, India.
authors.forename: P
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Pharmacology Division, Chandigarh College of Pharmacy, Landran, Mohali 140307, Punjab, India. Electronic address: cgc.ccp.rs@gmail.com.
authors.forename: R K
authors.initials: RK
authors.lastname: Sodhi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002712:Chlorides; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003704:Dementia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D000077297:Pregnane X Receptor; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D000682:Amyloid; D002712:Chlorides; D009573:Nitrites; D018697:Nootropic Agents; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D017392:Thiobarbituric Acid Reactive Substances; D000077410:Aluminum Chloride; D009195:Peroxidase; D000110:Acetylcholinesterase; D005978:Glutathione; D007654:Ketoconazole; D012293:Rifampin
keywords: Alzheimer’s disease; aluminum chloride; amyloid beta; dementia; pregnane X receptors; rifampicin