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Memory recuperative potential of rifampicin in aluminum chloride-induced dementia: role of pregnane X receptors.

Neuroscience 2015 March 13
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.

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