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.