Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity.
OBJECTIVE
The present study has been designed to investigate the involvement of the nitric oxide mechanism in the protective effect of lycopene against 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats.


METHODS
The present experimental protocol design includes systemic 3-nitropropionic acid (10mg/kg i.p) treatment for 14 days. Lycopene (2.5, 5 and 10mg/kg) was given orally, once a day, 1h before 3-nitropropionic acid treatment for 14 days. Body weight and behavioral parameters (locomotor and rotarod activity) were assessed on 1st, 5th, 10th and 15th day post-3-nitropropionic acid administration. Malondialdehyde, nitrite concentration, superoxide dismutase and catalase levels were measured on the 15th day in the striatum, cortex and hippocampus. Mitochondrial enzyme complexes were also assessed in these brain areas. Systemic 3-nitropropionic acid treatment significantly reduced body weight, locomotor activity and oxidative defense. The mitochondrial enzyme activities were also significantly impaired in the examined brain regions in 3-nitropropionic acid-treated animals.


RESULTS
Lycopene (2.5, 5 and 10mg/kg) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-nitropropionic acid-treated group. l-arginine (50mg/kg) pretreatment with a sub-effective dose of lycopene (5mg/kg) significantly attenuated the protective effect of lycopene. Furthermore, L-NAME (10mg/kg) pretreatment with a sub-effective dose of lycopene (5mg/kg) for 14 days significantly potentiated the protective effect.


CONCLUSIONS
The results of the present study suggest that the nitric oxide modulation is involved in the protective effect of lycopene against 3-NP-induced behavioral, biochemical and cellular alterations in rats.
Kumar
Puneet
P
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Kalonia
Harikesh
H
Kumar
Anil
A
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002338:Carotenoids / Q000494:pharmacology*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D004396:Coloring Agents; D003576:Electron Transport Complex IV / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D000077276:Lycopene; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009245:NADH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D016588:Anticarcinogenic Agents; D004396:Coloring Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009573:Nitrites; D009574:Nitro Compounds; D011422:Propionates; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D002338:Carotenoids; D002374:Catalase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; C022616:thiazolyl blue; C015392:3-nitropropionic acid; D000077276:Lycopene