Ibuprofen and lipoic acid diamide as co-drug with neuroprotective activity: pharmacological properties and effects in beta-amyloid (1-40) infused Alzheimer's disease rat model.
Both oxidative stress and inflammation are elevated in brains of Alzheimer's disease patients, but their pathogenic significance still remains unclear. Current evidence support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease, and ibuprofen has the strongest epidemiological support. In the present work our attention was focused on (R)-alpha-lipoic acid considered as a potential neuroprotective agent in Alzheimer's disease therapy. In particular, we investigated a new co-drug (1) obtained by joining (R)-alpha-lipoic acid and ibuprofen via a diamide bond, for evaluating its potential to antagonize the deleterious structural and cognitive effects of beta-amyloid (1-40) in an infused Alzheimer's disease rat model. Our results indicated that infusion of beta-amyloid (1-40) impairs memory performance through a progressive cognitive deterioration; however, ibuprofen and co-drug 1 seemed to protect against behavioural detriment induced by simultaneous administration of beta-amyloid (1-40) protein. The obtained data were supported by the histochemical findings of the present study: beta-amyloid protein was less expressed in 1-treated than in ibuprofen and (R)-alpha-lipoic acid alone-treated cerebral cortex. Taken together, the present findings suggest that co-drug 1 treatment may protect against the cognitive dysfunction induced by intracerebroventricular infusion of beta-amyloid (1-40) in rats. Thus, co-drug 1 could prove useful as a tool for controlling Alzheimer's disease-induced cerebral amyloid deposits and behavioural deterioration.
Di Stefano
A
A
Dipartimento di Scienze del Farmaco, Università G. d'Annunzio, Chieti, Italy. adistefano@unich.it
Sozio
P
P
Cerasa
L S
LS
Iannitelli
A
A
Cataldi
A
A
Zara
S
S
Giorgioni
G
G
Nasuti
C
C
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D007052:Ibuprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000008:administration & dosage*; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D008063:Thioctic Acid; D007052:Ibuprofen