Protective effects of epigallocatechin gallate following 3-nitropropionic acid-induced brain damage: possible nitric oxide mechanisms.
BACKGROUND
The role of oxidative stress has been well known in neurodegenerative disorders. 3-Nitropropionic acid (3-NP) is a plant-based mycotoxin that produces HD like symptoms in animals. Oxidative stress and nitric oxide mechanisms have been recently proposed in the 3-NP-induced neurotoxicity. Epigallocatechin gallate (EGCG) is one of the major components of green tea, known for its potent antioxidant activity. Besides, neuroprotective effect of EGCG has also been suggested in different experimental models.


OBJECTIVE
The present study has been designed to examine possible effect of EGCG against 3-NP induced behavioral, oxidative stress, mitochondrial dysfunction, and striatal damage in rats and its possible interaction with nitric oxide modulators.


METHODS
Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, grip strength, oxidative defense (raised levels of lipid peroxidation, nitrite concentration, depletion of antioxidant enzyme), and mitochondrial enzymes activity in striatum, cortex, and hippocampal regions of the brain.


RESULTS
Fourteen days of EGCG pretreatment (10, 20, and 40 mg/kg) significantly attenuated behavioral alterations, oxidative damage, mitochondrial complex enzymes dysfunction, and striatal damage in 3-NP-treated animals. L-arginine (50 mg/kg) pretreatment with sub-effective dose of EGCG (20 mg/kg) significantly reversed the protective behavioral, biochemical, cellular, and histological effects of EGCG. However, L-NAME (10 mg/kg) pretreatment with EGCG (20 mg/kg) significantly potentiated the protective effect of EGCG which was significant as compared to their effect per se.


CONCLUSIONS
The present study shows that EGCG attenuate 3-NP-induced neurotoxicity, and nitric oxide modulation might be involved in its protective action.
Kumar
Puneet
P
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160014, India.
Kumar
Anil
A
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009498:Neurotoxins / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D009574:Nitro Compounds / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; C015392:3-nitropropionic acid