Cyclooxygenase inhibitors: a novel direction for Alzheimer's management.
Journal Title: Pharmacological Reports - Year 2008, Vol 60, Issue 5
Abstract
Research in Alzheimer's disease (AD) currently includes various cellular, molecular, genetic, clinical and therapeutic approaches. The cytopathological significance of oxidative damage has been studied in neurons of AD patients. Many epidemiological studies suggest that use of non-steroidal anti-inflammatory drugs (NSAIDs) delay or slow the clinical expression of AD, and anti-oxidant properties of NSAIDs have also been previously described. Therefore, in this study we examined the role of various cyclooxygenase (COX)-1 and COX-2 inhibitors (NSAIDs) in a rat model of aluminum-induced oxidative stress to mimic AD-like conditions. We found that the animals receiving aluminum treatment for one month (4.2 mg/kg, ip) had highly elevated levels of reactive oxygen species (expressed as malondialdehyde - MDA). Moreover, treatment with the COX-2 inhibitor, rofecoxib (0.83 mg/kg, po), was able to significantly reduce this oxidative stress (p < 0.05 when compared to aluminum treatment alone on MDA levels). But, nonspecific COX inhibitors (flurbiprofen, 0.83 mg/kg twice a day po and ibuprofen, 100 mg/kg, po), did not protect again oxidative stress. Thus, in agreement with earlier epidemiological studies, we propose that COX-2 specific NSAIDs may be beneficial in AD management. Further experimental work towards identifying the most efficacious COX-2 inhibitors, as well as the mechanism of action and the optimal dosage regimen should be executed.
Authors and Affiliations
Manish Nivsarkar, Aryamitra Banerjee, Harish Padh
Keywords
Related Articles
- EP ID EP82939
- DOI -
- Views 87
- Downloads 0
5-HT-induced depression of the spinal monosynaptic reflex potential utilizes different types of 5-HT receptors depending on Mg2+ availability.
Receptor subtypes involved in the 5-hydroxytryptamine (5-HT)-induced depression of synaptic transmission in neonatal rat spinal cords in vitro were evaluated in the absence or presence of Mg(2+) in the medium. Stimulatio...
Role of nitric oxide in the development of tolerance to diazepam-induced motor impairment in mice.
Chronic treatment with the benzodiazepines is well known to produce tolerance, which has been extensively documented to be attributed to modifications in the gamma-aminobutyric acid (GABA)ergic neurotransmission. However...
Lack of the antianxiety-like effect of (S)-3,4-DCPG, an mGlu8 receptor agonist, after central administration in rats.
Substances acting as agonists of group III mGlu receptors were shown to induce an antianxiety-like effect after intrahippocampal administration to rats. The purpose of the present study was to establish whether the selec...
Effects of endothelin-1 on prevention of microvascular endothelium injuries in hemorrhagic shock in rats.
The aim of this study was to examine the effects of posthemorrhagic hypovolemia and hypotension upon the microvascular endothelial cells and on activity of antioxidant enzymes in blood, and to investigate the influence o...
Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex.
The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated...