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Animal Models
Author(s) -
R Grondin,
D Gwost,
P Hardy,
W Kaemmerer,
M Kaytor,
M Maier,
L Nechev,
B Nelson,
W Querbes,
Q Chen,
P Tan,
P Hadwiger,
M John,
M Solomon,
J Costigan,
G Wang,
Y Fan,
R Pandey,
K Charisse,
M Adams,
G Stewart,
M Manoharan,
V Kotelianski
Publication year - 2009
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2009.01224.x
Subject(s) - citation , computer science , medicine , library science
Background: Huntington’s disease is a progressive neurodegenerative disorder which is currently being treated symptomatically with a limited effectiveness. 3-nitropropionic acid is a well known mycotoxin produces Huntington’s disease like symptoms in animals. Recent reports suggest that oxidative stress and nitric oxide mechanism are involved in 3-nitropropionic acid induced neurotoxicity. Therefore, aim of present study was to examine possible role of epigallocatechin gallate (EGCG), a catechin-base flavonoid derived from green tea against 3-nitropropionic acid induced behavioural, oxidative stress and mitochondrial dysfunction in rats and its possible interaction with nitric oxide modulators. Materials and methods: Systemic 3-nitropropionic acid (10 mg/kg) administration for 14 days significantly induced Huntington’s disease like symptoms in rats as indicated by impairment in locomotor activity, body weight, grip strength, oxidative damage (elevated levels of lipid peroxidation, nitrite concentration, depletion of antioxidant enzyme levels) and mitochondrial dysfunction (complex –I, II, and IV) in striatum, cortex and hippocampal regions of brain. Results: EGCG pretreatment (10, 20 and 40 mg/kg) significantly attenuated behavioural alterations, oxidative stress and mitochondrial dysfunction in 3-NP treated group. However, L-arginine (50 mg/kg) pretreatment with sub effective dose of EGCG (20 mg/kg) significantly reversed protective effect of EGCG. Whereas L-NAME (10 mg/kg), a NOS inhibitor 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 conclusion of the present study showed that nitric oxide modulation might be involved in the protective effect of EGCG. Study further highlights the therapeutic potential of EGCG against Huntington’s like condition. Acknowledgment: The Senior Research Fellowship (Puneet Kumar) of the Indian Council of Medical Research (ICMR), New Delhi, is gratefully acknowledged.