Neuropharmacology and analgesiaLycopene protects against memory impairment and mito-oxidative damage induced by colchicine in rats: An evidence of nitric oxide signaling

Oxidative-nitrosative stress and mitochondrial dysfunction plays an important role in the onset of various neurodegenerative diseases. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Present study was designed to evaluate the possible nitric oxide mechanism in protective effects of lycopene against the colchicine induced cognitive impairment and mito-oxidative damage in rats. Wistar rats were received i.c.v. colchicine (15 µg/5 µl). Lycopene (2.5 and 5 mg/kg), NO modulators e.g. l-Arginine (50 mg/kg) l-NAME (5 mg/kg) administered for 21 days. Behavioural alterations were assessed in between study period. Animals were killed immediately following the last behavioral session, and mitochondrial enzymes, oxidative parameters, inflammatory mediators (TNF-α, IL-6) and caspase-3 activity were measured. I.C.V. administration of colchicine impaired memory performance in Morris water maze, oxidative defense and mitochondrial complex enzymes activities as compared to sham group. A significant increase of TNF-α, IL-6 and caspase-3 activity in hippocampus and cortex was also noted. Chronic treatment lycopene significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers and apoptosis in colchicine treated rats. Further, l-arginine pretreatment with sub effective dose of lycopene significantly reversed the protective effect of lycopene. However, l-NAME pretreatment with sub effective dose of lycopene significantly potentiated the protective effect of lycopene which was significant as compared to their effect per se. These results suggest that lycopene exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating nitric oxide pathways. Thus, lycopene may be used as therapeutic agent in preventing complications in memory dysfunction.

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