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To evaluate the combinational effect of Ethyl Pyruvate, Berberine and Poloxamer 188 on 3 nitropropionic acid induced Huntingtons disease

Volume No : (2018) Volume: 06 Issue : 30 Year : 2018 Page No: 32-37

Authors : Pallavi Bhosle, Pravinkumar Bhutada

Abstract :

The present study is undertaken to study the combinational effect of ethyl pyruvate, berberine, and poloxamer 188 on 3-nitropropionic acid (3NP)-induced Huntington’s disease. 3NP is a well-versed experimental model to study Huntington’s disease (HD)-induced motor, memory, and mitochondrial dysfunctions. Ethyl pyruvate, berberine, and poloxamer 188 are reported to exhibit a neuroprotective effect in various animal models. Moreover, berberine is reported to have a protective effect on memory dysfunction. In addition, poloxamer-188 and ethyl pyruvate reduce muscular atrophy, neuronal loss, and neuroinflammation. These evidences suggest that either single or combination of these agents may protect against 3NP model. Administration of 3NP (10 mg/kg) for 14 days in male Wistar rats significantly induced HD-like symptoms in rats as indicated by reduced locomotor activity, body weight, grip strength, oxidative defense, cognition, and mitochondrial complex enzymes activities in striatum, cortex, and hippocampus. All the behavioral and biochemical studies on control and treatment groups were done after 14 days. Marked elevation in lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and lipid peroxidation was also observed. Furthermore, a decrease in the levels of reduced glutathione was noted. However, pretreatment of combination (ethyl pyruvate [40 mg/kg], berberine [50 mg/kg], and poloxamer 188 [40 mg/kg]) significantly attenuated behavioral alterations, oxidative stress, neuronal loss, and mitochondrial enzymes complex dysfunction in 3NP-treated group and potentiates their respective protective effects. In conclusion, a combination of ethyl pyruvate, poloxamer 188, and berberine could be used to manage behavioral and biochemical alterations in HD than either of single drug therapy.

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