Role of neuroinflammatory mediators particularly
cyclooxygenase (COX),
lipoxygenase (LOX), have been well suggested in the pathophysiology of
neurodegenerative disorders.
Rofecoxib is a selective
cyclooxygenase 2 enzymes belongs to non-steroidal anti-inflammatory drug, commonly called as
coxibs. Whereas,
caffeic acid (3,4-dihydroxycinnamic acid) is one of the natural phenolic compounds and reported to inhibit
5-lipoxygenase (5-LOX) activity as one of mechanisms. Present study has been designed to investigate the effects of
rofecoxib,
caffeic acid and its potentiation by
galantamine against intrahippocampal
kainic acid-induced
cognitive impairment, oxidative damage and mitochondrial respiratory
enzyme alterations in rats.
Kainic acid (KA) was administrated in the hippocampus region of rat brain. Various behavioral (locomotor activity and memory performances were assessed by using actophotometer and Morris water maze respectively) followed by oxidative stress, mitochondrial
enzyme complex were assessed. Intrahippocampal administration of KA significantly impaired locomotor activity, memory performance, mitochondrial
enzyme complexes and caused oxidative stress as compared to
sham treatment.
Rofecoxib (5 and 10mg/kg),
caffeic acid (5 and 10mg/kg), Gal (2.5 and 5mg/kg) treatment for 14 days significantly improved locomotor activity, memory retention and oxidative defense (as evidenced by decrease lipid peroxidation,
nitrite, increased
superoxide dismutase activity and redox ratio) in hippocampus. Besides, alterations in the levels of mitochondrial
enzymes and
acetylcholine esterase enzyme were significantly restored by
rofecoxib and
caffeic acid as compared to control. Further, combination of
rofecoxib (5mg/kg) with
caffeic acid (5mg/kg) and lower dose of gal (2.5mg/kg) with
rofecoxib (5mg/kg) treatments significantly potentiated their protective effect which was significant as compared to their effect per se. The results of the present study suggest that
galantamine potentiates the protective effect of
rofecoxib and
caffeic acid against
kainic acid induced
cognitive impairment and associated oxidative damage.