title: Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats.
abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder with a spectrum of cognitive, behavioral, and motor abnormalities. The mitochondrial toxin 3-nitropropionic acid (3-NP) effectively induces specific behavioral changes, primarily manifested as prepulse inhibition (PPI) deficit of acoustic startle stimuli, and selective striatal lesions in rats and primates mimicking those in HD. The implications of nitric oxide in a variety of neurodegenerative diseases attract attention to study the possible role of flavonoids in interaction with nitric oxide pathways involved in HD. The present study investigates the potential effect of hesperidin, a flavanone group member, on 3-NP-induced behavioral, neurochemical, histopathological and cellular changes. Systemic administration of 3-NP to rats for 5 days (20 mg/kg) caused reduction of locomotor activity by days 2 and 5, 55% deficit of PPI response, elevation of cortical, striatal and hippocampal malondialdehyde (MDA) levels by 63%, 41% and 56%, reduction of respective catalase activity by 50%. Immunohistochemical staining of cortices, striata and hippocampi showed patches of iNOS positive cells. Electron microscopic ultrastructural examination showed marked mitochondrial swelling, perivascular edema and shrunken nerve cells. Pretreatment with hesperidin (100 mg/kg) ahead of 3-NP prevented any changes of locomotor activity or PPI response, slightly increased cortical, striatal and hippocampal MDA levels by 10% and reduced respective catalase activity by 22%, 20% and 5%. Only few iNOS positive cells were detected in sections from rats pretreated with hesperidin which also reduced cellular abnormalities induced by 3-NP. This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations. Such neuroprotection can be referred to its antioxidant and anti-inflammatory activities.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors: Esther T
authors: ET
authors: Menze
authors: Mariane G
authors: MG
authors: Tadros
authors: Ahmed M
authors: AM
authors: Abdel-Tawab
authors: Amani E
authors: AE
authors: Khalifa
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D002374:Catalase / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006569:Hesperidin / Q000627:therapeutic use*; D007266:Inhibition, Psychological; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D013997:Time Factors
chemical_list: D003292:Convulsants; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D006569:Hesperidin; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; C015392:3-nitropropionic acid