Curcumin is protective against phenytoin-induced cognitive impairment and oxidative stress in rats

• Published in: Brain research 2009-11, Vol.1301, p.52-60
• Main Authors: Reeta, K.H, Mehla, Jogender, Gupta, Yogendra Kumar
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anticonvulsants - toxicity; Anticonvulsants. Antiepileptics. Antiparkinson agents; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cognition - drug effects; Cognition Disorders - chemically induced; Cognition Disorders - prevention & control; Cognitive impairment; Curcumin; Curcumin - administration & dosage; Dose-Response Relationship, Drug; Exploratory Behavior - drug effects; Glutathione - metabolism; Lipid Peroxidation - drug effects; Male; Malondialdehyde - metabolism; Maze Learning - drug effects; Medical sciences; Neurology; Neuropharmacology; Oxidative stress; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Phenytoin; Phenytoin - blood; Phenytoin - toxicity; Rats; Rats, Wistar; Retention (Psychology) - drug effects
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.09.027

Abstract The present study investigates the effect of chronic curcumin administration on phenytoin-induced cognitive impairment and oxidative stress in rats. Male Wistar rats were administered drugs/vehicle for 21 days. Learning and memory was evaluated using the passive avoidance paradigm and the elevated plus maze. On day 21, serum phenytoin concentrations and whole brain malondialdehyde (MDA) and glutathione (GSH) levels were estimated. Phenytoin (75 mg/kg, i.p.) produced significant deficits in learning/memory as indicated by the significant increase in retention transfer latency in elevated plus maze test and a significant decrease in retention latency in the passive avoidance paradigm. Chronic administration of phenytoin also produced significant elevations in brain MDA and reduction of brain GSH levels. Curcumin (100, 200 and 300 mg/kg, orally), when administered with phenytoin, significantly prevented phenytoin-induced cognitive impairment and oxidative stress in a dose-dependent manner. There were no significant differences in the serum levels of phenytoin in any of the treatment groups. This study demonstrates that curcumin is effective in preventing phenytoin-induced cognitive impairment and oxidative stress in rats without altering the serum phenytoin levels. This suggests the potential of adjuvant curcumin therapy in ameliorating cognitive impairment caused by chronic phenytoin therapy.