Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity

AimThe 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.Main methodsThe present experimental protocol design includes systemic 3-nitropropionic acid (10 mg/kg i.p) treatment for 14 days. Lycopene (2.5, 5 and 10 mg/kg) was given orally, once a day, 1 h 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.Key findingsLycopene (2.5, 5 and 10 mg/kg) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-nitropropionic acid-treated group. l-arginine (50 mg/kg) pretreatment with a sub-effective dose of lycopene (5 mg/kg) significantly attenuated the protective effect of lycopene. Furthermore, L-NAME (10 mg/kg) pretreatment with a sub-effective dose of lycopene (5 mg/kg) for 14 days significantly potentiated the protective effect.SignificanceThe 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.