Protective effect of rivastigmine against 3-nitropropionic acid-induced Huntington's disease like symptoms: possible behavioural, biochemical and cellular alterations

Puneet Kumar, Anil Kumar
European Journal of Pharmacology 2009 August 1, 615 (1): 91-101
3-Nitropropionic acid inhibits succinate dehydrogenase, complex II enzyme in the mitochondrial respiratory chain that leads to cellular energy deficit and oxidative stress. Huntington's disease is characterized by abnormal body movements (chorea) and cognitive dysfunctions. Rivastigmine, a well known cholinesterase inhibitor used in the management of Alzheimer's disease in a clinical practice. Recent clinical studies suggest the potential role of rivastigmine in the management of Huntington's disease. The present study has been designed to explore the possible role of rivastigmine against 3-nitropropionic acid induced behavioral, biochemical and cellular alterations. Intraperitoneal administration of 3-nitropropionic acid (10 mg/kg for 14 days) caused significant loss in body weight, motor in coordination (locomotor activity and rota rod performance) and poor memory retention in Morris water maze and elevated plus maze performance tasks as compared to vehicle treated animals. Biochemical analysis revealed significant increase in lipid peroxidation, nitrite concentration and depleted superoxide dismutase, catalase levels and alterations in mitochondrial complex enzymes (I, II, IV and MTT assay) in the different regions (striatum, cortex and hippocampus) of rat brain. Rivastigmine (0.5, 1 and 2 mg/kg, orally) once daily treatment for a period of 14 days significantly improved motor performance and cognitive task in both Morris water maze and elevated plus maze tests. Further, rivastigmine treatment significantly attenuated oxidative damage and improved mitochondrial complexes enzyme activities in different regions (striatum, cortex and hippocampus) of rat brain. The results show that rivastigmine could be used as an effective therapeutic agent in the management of Huntington's disease and related conditions.

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