title: Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway.
abstract: Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediated regulation of cellular antioxidant production and the anti-inflammatory mechanism play an important role in neuroprotection against neurodegenerative diseases. Naringin a citrus flavonone, has been reported to possess neuroprotective effect against Huntington's disease, and other neurodegenerative disorders, however the mechanisms underlying its beneficial effects on 3-nitropropionic acid (3-NP)-induced neurodegeneration are poorly defined. The objective of the present study was to investigate the neuroprotective role of naringin and delineate the mechanism of action on 3-NP-induced neurodegeneration. Rats were injected with 3-NP (10mg/kg body weight/day, i.p.) for 2 weeks to develop neurodegeneration, while naringin (80 mg/kg body weight/day, orally) was administered throughout the experimental period, 1h prior to 3-NP exposure. Thereafter rats were euthanized for biochemical, histological, and molecular studies. Treatment with naringin ameliorated the reduced glutathione/oxidized glutathione ratio with concomitant decrease in the levels of hydroxyl radical, hydroperoxide and nitrite in 3-NP-induced rats. Nissl staining and transmission electron microscopic studies showed that naringin modulated 3-NP-induced histological changes. Naringin induces NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutathione S-transferase P1 and gamma-glutamylcysteine ligase mRNA expressions through the activation of Nrf2 and decreased the expressions of pro-inflammatory mediators like tumour necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. These results indicate that naringin might be beneficial in mitigating 3-NP-induced neurodegeneration through the enhancement of phase II and antioxidant gene expressions via Nrf2 activation; thereby modulating the oxidative stress and inflammatory responses.
authors.affiliation: Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: K
authors.initials: K
authors.lastname: Gopinath
authors.forename: G
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D003292:Convulsants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control*; D044950:Flavanones / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000150:complications; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D011422:Propionates / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D003292:Convulsants; D044950:Flavanones; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005978:Glutathione; C005274:naringin; C015392:3-nitropropionic acid; D019803:Glutathione Disulfide