NEUROPROTECTIVE EFFECT OF RESVERATROL ON VALPROIC ACID INDUCED OXIDATIVE STRESS AUTISM IN SWISS ALBINO MICE
Abstract
The present research work is aimed to investigate the anti-oxidant/neuroprotective role of Resveratrol in reversing the valproic acid induced autism in postnatal swiss albino mice. Separate 13 day old/ Post natal day (PND) 13 swiss albino mice of either sex into 5 groups, each group consists of six mice of either sex, groups namely Group I - Control, Group II - Resveratrol, Group III - Negative control, Group IV & V - Resveratrol treatment groups. On PND 14 administer single dose of Valproic acid (VPA) or Sodium Valproate (400 mg/kg, subcutaneously) to III, IV & V groups to induce autism. Treatment is given in two doses 10 mg/kg, intraperitoneally (i.p) as Low dose and 40 mg/kg, i.p as High dose from the 13th day to the end of study. Assessment of autism is done by different behavioral screening methods during PND 14 to 40. Treatment with resveratrol significantly decline the autism symptoms compared with negative control. At the end of study on PND 41 all the animals were sacrificed to assess the biochemical estimations like Anticholinesterase enzyme, Total Protein, antioxidant enzyme (Catalase, Superoxide and Glutathione) activity and cerebellar histopathological examination. Treatment with Resveratrol has shown a significant beneficial difference on behavioral alterations, oxidative markers, neurotransmitters, and restoration of the altered purkinje cells of autism. This research work we conclude that resvertrol have a potent anti-oxidant, neuroprotective, anxiolytic, learning & memory enhancing agent against valproic acid induced autism.
Keywords:
Valproic acid, Oxidative stress, Autism, Resveratrol, Neuroprotective effectDOI
https://doi.org/10.25004/IJPSDR.2018.100301References
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33. Wagner CG, Reuhl KR, Cheh M, et al. A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. J. AutismDev. Disord. 2006; 36:779–793.
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35. Darine Fray N Mabunga, Edson Luck T Gonzales, Ji-Woonkim, et al. Explorig the validity of valproic acid animal model of Autism. Experimental Neurobiology. 2015; 24(4):285-300.
36. Morrison AS, Lyketsos C. The pathology of Alzheimer's disease and direction in treatment. Adv. Stud. Nurs. 2005; 3:256–270.
37. Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. New England Journal of Medicine. 2001; 344:1132-1138.
38. Parellada M, Moreno C, Mac-Dowell K, et al. Plasma antioxidant capacity is reduced in Asperger Syndrome. J Psychiatr Res. 2011; 46(3):394-401.
39. Emanuel Dicicco-Bloom, Catherine Lord, Lonnie Zwaigenbaum, et al. The Developmental Neurobiology of Autism Spectrum Disorder. The Journal of Neuroscience. 2006; 26(26):6897-6906.
2. Lord C, Risi S, Lambrecht L, et al. The Autism Diagnostic Observation Schedule Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of autism and developmental disorders. 2000; 30:205-23.
3. Gadia CA, Tuchman R, Rotta NT. Autism and pervasive developmental disorders. Journal de Pediatria. 2004; 80(2):S83-S94.
4. Llaneza DC, DeLuke SV, Batista M, et al. Communication, interventions, and scientific advances in autism: a commentary. Physiol. Behav. 2010; 100:268–276.
5. Bushnell PJ. Environmental influences and emerging mechanisms in the etiology of autism. Neurotoxical Teratol. 2013; 36:1-2.
6. Cohly HH, Panja A. Immunological findings in autism. Int. Rev. Neurobiol. 2005; 71:317-341.
7. London EA. The environment as an etiologic factor in autism: A new direction for research, Environ. Health Perspect. 2000; 108:401-404.
8. Mutter, Naumann J, Schneider R, et al. Mercury and autism: accelerating evidence? Neuro. Endocrinol. 2005; Lett 26:439-446.
9. Browne, TR. Valproic acid. N Engl J Med. 1980; 302:661–666.
10. Isojavi JI, Tauboll E, Herzog AG. Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS Drugs. 2005; 19:207–223.
11. Zarate Jr CA, Tohen M, Narendran R. The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study. J Clin Psychiatr.1999; 60:232–236.
12. Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006; 13:171–181.
13. Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. Journal of Toxicology and Environmental Health. 2006; Part B 9:485-499.
14. Sweeten TL, Posey DJ, Shankar S, et al. High nitric oxide production in autistic disorder: a possible role for interferon-γ Biological psychiatry. 2004; 55:434-437.
15. Jang J, Park D, Shin S, et al. Antiteratogenic effect of resveratrol in mice exposed in utero to 2,3,7, 8-tetrachlorodibenzo-p-dioxin. European Journal of Pharmacology. 2008; 591:280–283.
16. Ates O, Cayli SR, Yucel N. Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats. Journal of Clinical Neurosceinces. 2007; 14:256-260.
17. Venturini CD, Merla S, Souto AA, et al. Resveratrol and red wine function as antioxidant in the nervous system without cellular proliferation effects during experimental diabetes. Oxidative Medicine and Cellular Longevity. 2010; 3:434-441.
18. Ming X, Cheh MA, Halladay AK, et al. Evidence of oxidative stress in autism derived from animal models. Am.J. Biochem. Biotechnol. 2008; 4:218–225.
19. Schneider T, Przewłocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology. 2005; 30: 80–89.
20. Elder GA, Ragnauth A, Dorr N, et al. Increased locomotor activity in mice lacking the low-density lipoprotein receptor. Behav. Brain Res. 2008; 191:256–265.
21. Schneider T, Turczak J, Przewłocki R. Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: issues for a therapeutic approach in autism Neuropsychopharmacology. 2006; 31:36–46.
22. Matsuo N, Tanda Nakanishi K, et al. Comprehensive behavioral phenotyping of ryanodine receptor type 3 (RyR3) knockout mice: decreased social contact duration in two social interaction tests. Front. Behav. Neurosci. 2009; 3:1–13.
23. Maria RR, Ivan I, Maria CBR, et al. Effect of lyophilized Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res. 2005; 52:457–462.
24. Parle M, Vasudevan M, Singh N. Swim every day to keep Dementia away. Journal of Sports Science and Medicine. 2005; 4:37-46.
25. Morris R. Developments of a water-maze procedure for studying spatial learching in the rat. J Neurosci Methods. 1984; 11(1):47-60.
26. Markram K, Rinaldi T, Mendola D, et al. Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism. Neuropsychopharmacology. 2007; 33:901–12.
27. Ellman L, Courtney KD, Valentino A, et al. Anewandrapid colorimetric determination of acetyl cholinesterase activity. Biochem. Pharma – col. 1961; 7:88–95.
28. Vos G, Sachsse K. Red cell and plasma cholinesterase activities in micro samples of human and animal blood determined simultaneously by a modifiedacetylthiocholine/DTNB procedure. Toxicol Appl Pharmacol. 1970; 16:764–72.
29. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1):70–77.
30. Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clin. Chim. Acta. 1991; 196:143–152.
31. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur Jf Biochem. 1974; 47:469–474.
32. Chalon Tarkiainen J, Garreau L, Hall H, et al. Pharmacological characterization of N, N-dimethyl-2-(2-amino-4-methylphenyl thio benzyl amine as a ligand of the serotonin transporter with high affinity. J Pharmacol Exp Ther. 2003; 304(1):81-87.
33. Wagner CG, Reuhl KR, Cheh M, et al. A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. J. AutismDev. Disord. 2006; 36:779–793.
34. Banji D, Banji O, Abbagoni S, et al. Amelioration of behavioral aberrations and oxidative markers by green tea extract in valproate induced autism in animals. Brain Research. 2011; 1410:141–151.
35. Darine Fray N Mabunga, Edson Luck T Gonzales, Ji-Woonkim, et al. Explorig the validity of valproic acid animal model of Autism. Experimental Neurobiology. 2015; 24(4):285-300.
36. Morrison AS, Lyketsos C. The pathology of Alzheimer's disease and direction in treatment. Adv. Stud. Nurs. 2005; 3:256–270.
37. Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. New England Journal of Medicine. 2001; 344:1132-1138.
38. Parellada M, Moreno C, Mac-Dowell K, et al. Plasma antioxidant capacity is reduced in Asperger Syndrome. J Psychiatr Res. 2011; 46(3):394-401.
39. Emanuel Dicicco-Bloom, Catherine Lord, Lonnie Zwaigenbaum, et al. The Developmental Neurobiology of Autism Spectrum Disorder. The Journal of Neuroscience. 2006; 26(26):6897-6906.
Published
01-05-2018
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“NEUROPROTECTIVE EFFECT OF RESVERATROL ON VALPROIC ACID INDUCED OXIDATIVE STRESS AUTISM IN SWISS ALBINO MICE”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 10, no. 3, May 2018, pp. 103-10, https://doi.org/10.25004/IJPSDR.2018.100301.
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“NEUROPROTECTIVE EFFECT OF RESVERATROL ON VALPROIC ACID INDUCED OXIDATIVE STRESS AUTISM IN SWISS ALBINO MICE”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 10, no. 3, May 2018, pp. 103-10, https://doi.org/10.25004/IJPSDR.2018.100301.
