Effect of rutin against a mitochondrial toxin, 3-nitropropionicacid induced biochemical, behavioral and histological alterations-a pilot study on Huntington's disease model in rats.

Abstract

Dietary compounds like flavonoids may offer protection against neurodegeneration. Huntington's disease (HD) is a neurodegenerative disorder characterized by symptoms like chorea and dementia. 3-Nitropropionic acid (3-NP), a Succinate dehydrogenase (SDH) inhibitor produces behavioral, biochemical and histological changes in the striatum, mimics HD in animals and humans. The present study was designed to examine the protective activity of Rutin (RT), a primary flavonoid from citrus fruits, green tea on 3-NP induced experimental model of HD in rats. Rats were pretreated with Rutin, a potent antioxidant (25 and 50mg/kg b.w.) orally prior to the intraperitoneally (i.p.) administration of 3-NP (10mg/kg b.w.) for 14days. Behavioral assessments were carried out on 5th, 10th and 15th day after 3-NP treatment. Body weight, biochemical and histological studies were analyzed on 15th day. Systemic administration of 3-NP significantly reduced the body weight, locomotor activities (Rota rod, Open field test), memory (Morris water maze) and antioxidants such as Glutathione (GSH) levels, activities of Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione-S-transferase (GST), Glutathione reductase (GR). 3-NP also produces striatal damage by increased the levels of lipid peroxides, nitrite, Glial Fibrillary Acidic Protein (GFAP) and activity of Acetylcholine esterase (AchE). Thus, Rutin treatment of 25 and 50mg/kg b.w. has significantly restored all the biochemical, behavioral and histological alterations caused by the 3-NP through its antioxidant activity. The findings of our study indicates that Rutin may have an important role in protecting the striatum from oxidative/nitrosative insults caused by 3-NP. These results suggest that RT might be a drug of choice to treat HD.