title: Galantamine potentiates the protective effect of rofecoxib and caffeic acid against intrahippocampal Kainic acid-induced cognitive dysfunction in rat.
abstract: 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.
authors: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh 160014, India. kumaruips@yahoo.com
authors: Anil
authors: A
authors: Kumar
authors: Atish
authors: A
authors: Prakash
authors: Deeksha
authors: D
authors: Pahwa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D002109:Caffeic Acids / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005702:Galantamine / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity; D007783:Lactones / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009245:NADH Dehydrogenase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013450:Sulfones / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D007783:Lactones; D009573:Nitrites; D018697:Nootropic Agents; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D005702:Galantamine; C116926:rofecoxib; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D000110:Acetylcholinesterase; D005978:Glutathione; D007608:Kainic Acid; C040048:caffeic acid