title: Montelukast potentiates the protective effect of rofecoxib against  kainic acid-induced cognitive dysfunction in rats.
abstract: There is an evolving consensus that mild cognitive impairment (MCI) serves as a prodrome to Alzheimer's disease. Antioxidants and COX-2 (cyclo-oxygenase-2) inhibitors have also been reported to have beneficial effects against conditions of memory impairment. Newer drugs like cysteinyl leukotriene inhibitors have shown neuroprotective effect in animal models of ischemia. Thus, the present study purports to explore the potential role of montelukast (a cysteinyl leukotriene inhibitor) in concert with rofecoxib (COX-2 inhibitor) and caffeic acid (a 5-LOX inhibitor and potent antioxidant) against kainic acid induced cognitive dysfunction in rats. In the experimental protocol, kainic acid (0.4 μg/2 μl) in artificial cerebrospinal fluid (ACSF) was given intrahippocampally (CA3 region) to induce a condition similar to MCI. Memory performance was measured on days 10-14 and the locomotor activity was measured on days 1, 7 and 14. For estimation of biochemical, mitochondrial and histopathological parameters, animals were sacrificed on day 14, stored at -80 °C and the estimation was done on the 15th day. The treatment groups consisting of montelukast (0.5 and 1 mg/kg), rofecoxib (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) showed significant improvement in memory performance, oxidative stress parameters and mitochondrial function as compared to that of control (kainic acid treated), however, combination of montelukast with rofecoxib showed significant improvement in their protective effect. Thus the present study emphasizes the positive modulation of cysteinyl leukotriene receptor inhibition on COX (cyclooxygenase) and LOX (lipoxygenase) pathways in the control of the neuroinflammation in kainic acid induced cognitive dysfunction in rats.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160014, India. kumaruips@yahoo.com
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Atish
authors.initials: A
authors.lastname: Prakash
authors.forename: Deeksha
authors.initials: D
authors.lastname: Pahwa
authors.forename: Jitendriya
authors.initials: J
authors.lastname: Mishra
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002109:Caffeic Acids / Q000008:administration & dosage; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D003521:Cyclopropanes; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D007783:Lactones / Q000008:administration & dosage*; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009498:Neurotoxins / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides; D013450:Sulfones / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000085:Acetates; D000975:Antioxidants; D002109:Caffeic Acids; D052246:Cyclooxygenase 2 Inhibitors; D003521:Cyclopropanes; D007783:Lactones; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011804:Quinolines; D013440:Sulfides; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C116926:rofecoxib; D000110:Acetylcholinesterase; D005978:Glutathione; C093875:montelukast; D007608:Kainic Acid; C040048:caffeic acid