Neuroprotective effects of ascorbic acid against 3-NP induced Huntington’s disease in experimental rats
Abstract
Objective: The present study was designed to evaluate the neuroprotective effects of ascorbic acid against 3-nitropropionic acid (3-NP) induced huntington’s disease [HD] in rats and possible involvement of GABAA receptors.
Methods: 3-nitropropionic acid (10 mg/kg) was administered intraperitoneally (i.p) once daily for a period of 14 days to induce the symptoms of HD. In this study bicuculline was employed as an antagonist to confirm the involvement of GABA receptor. All the behavioural parameters were observed before drug administration and 24 hrs after first dose and 24 hrs after the last dose, that on the 15th day after the start of 3-NP treatment.
Results: Administration of ascorbic acid (200 mg/kg, i.p.) per se had no effect on acquisition, memory, motor activity and various biochemical parameters as compared to control group animals. Pre-treatment with ascorbic acid (100 mg/kg and 200 mg/kg, i.p.) once daily for a period of 14 days attenuated 3-NP induced motor and cognitive impairement together with improvement in biochemical parameters (↑GSH, ↓ MDA, ↓ AChE, ↓ MPO& ↓ iNOS) in a dose dependent manner in rats. Pre-treatment with bicuculline (1 mg/g, i.p.) once daily for a period of 14 days abolished the neuroprotective effects of ascorbic acid on 3-NP treated rats. In addition, histopathological changes in present study have further justified the approach.
Conclusion: The results of the present study demonstrate that ascorbic acid has shown neuroprotective effects against 3-NP induced behavioural and biochemical alterations similar to Huntington’s disease in rats and the said role of ascorbic acid involves the activation of GABAA receptors..
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2. Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 1993; 13: 4181-4192.
3. Bossi SR, Simpson JR, Isacson O. Age dependence of striatal neuronal death caused by mitochondrial dysfunction, Neuroreport 1993; 4: 73-76.
4. Pinto AC, Acuna AI, Beltran FA, -Diaz LT, Castro MA. Old things new view: Ascorbic acid protects the brain in neurodegenerative disorders. Int J Mol Sci 2015; 16: 28194–28217.
5. Kumar P, Kumar A. Neuroprotective effect of cyclosporine and FK506 againt 3 nitropropionic acid induced cognitive dysfunction and glutathione redox in rat: possible role of nitric oxide. Neurosci Res 2009; 63: 302-314.
6. Kumar A, Dogra S. Neuroprotective effect of Carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat. Pharmac Biochem Behav 2009; 92: 25-31.
7. SK Kulkarni. Hand Book of Experimental Pharmacology, 3rd edition, Vallabh Prakashan, 1999, 131-134
8. Reddy DS, Kulkarni SK. Possible role nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging- and dizocilpineinduced learning impairment. Brain Res 1998; 799: 215-229.
9. Nichans WG, Samuelson BJ. Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6:126-130.
10. Beutler E, Duran O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882.
11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein Measurement with the Folin Phenol Reagent. J Biol Chem 1951; 193: 265-275.
12. Green LC, Wagner DA, Godowsky J, Skipper PL, Wishnok JS, Tannenbaum, SR. Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 1982; 126:131-138.
13. Ellman GL, Courtney KD, Andres VJ, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88–90.
14. Koladiya RU, Jaggi AS, Singh N, Sharma BK. Beneficial effects of donepezil on vascular endothelial dysfunction-associated dementia induced by Lmethionine in rats. JHealth Sci 2009; 55: 215-225.
15. Krawisz JE, Sharon P, Stenson WF. Qualitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 1984; 87:1344-1350.
16. Clayden EC. Practical section cutting and staining, 5th Edition, Churchill, livingstone, Edinburgh and London
1971: 270.
17. Covarrubias-Pinto A, Moll P, Solis-Maldonado M, Acuna AI, Riveros A, Paz MM, Papic E, Beltrán FA, Cepeda, C, Concha II, et al. Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in huntington’s disease. Free Radic Biol Med 2015; 89: 1085-1096.
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