title: Effect of licofelone--a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats.
abstract: The present study was designed to investigate the effect of licofelone-a dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitor in intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficit and biochemical abnormalities in rats. ICV-STZ is a widely used model of sporadic Alzheimer's disease. In this study, STZ was administered intracerebroventricular (i.c.v.)-bilaterally 3 mg/kg in rats. The STZ-injected rats were treated with different doses of licofelone (2.5, 5, and 10 mg/kg, p.o.) for 21 days. Cognitive functions were assessed by using Morris water maze and passive avoidance task. Levels of malondialdehyde (MDA), nitrite, reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were determined to check oxidative stress and cholinergic function. Cytokine levels (IL-1β and TNF-α) were also determined as markers of neuroinflammation. Administration of STZ caused a significant increase in AChE activity and cognitive dysfunction. Increased oxidative stress and the proinflammatory cytokine levels were also observed following STZ administration in rats. Licofelone treatment attenuated STZ-induced cholinergic hypofunction and cognitive deficit in rats. In addition, licofelone attenuated STZ-induced oxidative stress and elevated cytokine levels. The cognitive enhancement following licofelone administration in STZ rats may be due to its ability to restore cholinergic functions or its antioxidant activity. These observed results suggest the therapeutic potential of dual COX/5-LOX inhibitors in neurodegenerative disorders associated with oxidative stress and cognitive impairment.
authors.affiliation: Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Sorabh
authors.initials: S
authors.lastname: Sharma
authors.forename: Ashwani
authors.initials: A
authors.lastname: Prashar
authors.forename: Rahul
authors.initials: R
authors.lastname: Deshmukh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001362:Avoidance Learning; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D008315:Malondialdehyde; D013311:Streptozocin; D000110:Acetylcholinesterase; D005978:Glutathione; C088092:licofelone