Toxicology International (Formerly Indian Journal of Toxicology)

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Neuroprotective Effect of Naringin on Acrylamideinduced Cytotoxicity in U87MG Cells and Wistar Rats: An in-vitro and in-vivo Study


Affiliations
1 Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati – 517502, Andhra Pradesh., India
2 Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur – 522019, Andhra Pradesh., India
     

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Acrylamide (ACR) is a potent neurotoxic to humans and animals. Neuroprotective effect of naringin was evaluated on ACR induced cytotoxicity using U87MG cells as in-vitro model and rat as in vivo model. ACR (50 mg/kg, i.p.) and Naringin (50 and 100 mg/kg) were administered to rats for 4 weeks. After 4 weeks, rats were sacrificed and sciatic nerves were isolated to determine the biochemical and apoptotic parameters. The exposure of U87MG cells to ACR reduced cell viability. Pretreatment of cells with 5–300 μg/ml naringin before ACR treatment significantly attenuated ACR cytotoxicity in a dose-dependent manner. Naringin down-regulated the Bax and upregulated the Bcl2 protein expression levels and also scavenged ACR induced free radicals in rats. In conclusion, our results indicated that pretreatment with naringin protected cells and rats from ACR-induced cytotoxicity and the neuroprotective effect was due to its antiapoptotic and antioxidant potential.

Keywords

Acrylamide, Apoptosis, Naringin, Neurotoxicity, Oxidative Stress, U87MG Cells.
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  • Zyzelewicz D, Nebesny E, Oracz J. Acrylamide-formation, physicochemical and biological properties. Bromatol Chem Toksykol. 2010; 43:415–27.

  • Jankowska JHJ, Potocki A. Acrylamide as a foreign substance in food (in Polish). Problemy Higieny I Epidemiologii. 2009; 90:171–4.

  • Dybing E, Sanner T. Risk assessment of acrylamide in foods. Toxicol Sci. 2003; 75:7–15. https://doi. org/10.1093/toxsci/kfg165. PMid:12805639.

  • Grob K, Biedermann M, Biedermann-Brem S, Noti A, et al. French fries with less than 100 µg/kg acrylamide. A collaboration between cooks and analysts. Eur Food Res Technol. 2003; 217:185–194. https://doi. org/10.1007/s00217-003-0753-9.

  • Cummins E, Butler F, Brunton N, Gormley R. Factors affecting acrylamide formation in processed potato products a simulation approach. 13th World Congress of Food Science & Technology 2006; Nantes: 719. https://doi.org/10.1051/IUFoST:20060719.

  • Lopachin RM. Acrylamide neurotoxicity: Neurological, morphological and molecular endpoints in animal models. Chemistry and safety of acrylamide in food 2005; New York: Springer.

  • Shipp A, et al. Acrylamide: Review of toxicity data and doseresponse analyses for cancer and noncancer effects. Critical Reviews in Toxicology. 2006; 36(6):481–608. https://doi.org/10.1080/10408440600851377. PMid:169 73444.

  • Tripoli E, Guardia ML, Giammanco S, Majo DD, Giammanco M. Citrus flavonoids: molecular structure, biological activity and nutritional properties: A review. Food Chem. 2007; 104:466–79. https://doi. org/10.1016/j.foodchem.2006.11.054.

  • Chen F, Zhang N, Ma X, Huang T, et al. Naringin alleviates diabetic kidney disease through inhibiting oxidative stress and inflammatory reaction. PLoS One. 2015. https://doi.org/10.1371/journal.pone.0143868. PMid:26619044 PMCid:PMC4664292.

  • Golechha M, Sarangal V, Bhatia J, Chaudhry U, et al. Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: Possible mechanisms of neuroprotection. Epilepsy Behav. 2014; 41:98–102. https://doi.org/10.1016/j.yebeh.2014.09.058. PMid:25461197.

  • Luo YL, Zhang CC, Li PB, Nie YC, et al. Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke. Int Immunopharmacol. 2012; 13:301–7. https://doi. org/10.1016/j.intimp.2012.04.019. PMid:22575871.

  • Ramesh E, Alshatwi AA. Naringin induces death receptor and mitochondria- mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol. 2013; 51:97–105. https://doi.org/10.1016/j. fct.2012.07.033. PMid:22847135.

  • Jeon SM, Park YB, Choi MS. Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin. Nutr. 2004; 23(5):1025–34. https://doi.org/10.1016/j.clnu.2004.01.006. PMid:15380892.

  • Gopinath K, Prakash D, Sudhandiran G. Neuroprotective effect of naringin, a dietary flavonoid against 3-nitropropionic acid-induced neuronal apoptosis. Neurochem In. 2011; 59(7):1066–73. https://doi. org/10.1016/j.neuint.2011.08.022. PMid:21945202.

  • Misra HP Fridovich J. The role of Superoxide anion in the auto oxidation of epinephrine and simple assay for superoxide dismutase. J Biol Chem. 1972; 247:3170–75. https://doi.org/10.1016/S0021-9258(19)45228-9.

  • Ohkawa H, Ohishi N Yagi K. Assay for lipid peroxides in animals and tissue by thiobarbituric acid reaction. Analatical Biochemistry. 1979; 95:351–8. https://doi. org/10.1016/0003-2697(79)90738-3.

  • Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82(1):70–7. https://doi.org/10.1016/00 03-9861(59)90090-6.

  • Lorentz K. Improved determination of serum calcium with Orthocresolpthalein complexone. Clin Chem Acta. 1982; 126:327–33. https://doi.org/10.1016/0009- 8981(82)90308-4.

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193:265–75. https://doi.org/10.1016/ S0021-9258(19)52451-6.

  • Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells. Cell Mol Neurobiol. 2012; 32:227–35. https://doi.org/10.1007/ s10571-011-9752-8. PMid:21901509.

  • Hosseinzadeh H, Tabeshpur J, Mehri S. Effect of saffron extract on acrylamide- induced toxicity: In vitro and in vivo assessment. Chin J Integr Med. 2014.

  • Esmaeelpanah E, Razavi BM, Hasani FV, Hosseinzadeh H. Evaluation of epigallocatechin gallate and epicatechin gallate effects on acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells. Drug Chem Toxicol. 2018; 41(4):441–8. https://doi.org/10.1080/01480545.2 017.1381108. PMid:29072525.

  • Kianfar M, Nezami A, Mehri S, Hosseinzadeh H, et al. The protective effect of fasudil against acrylamideinduced cytotoxicity in PC12 cells. Drug and Chemical Toxicology. 2018.p. 1–7. https://doi.org/10.1080/01480 545.2018.1536140. PMid:30574809.

  • Crack PJ, Taylor JM. Reactive oxygen species and the modulation of stroke. Free Radic Biol Med. 2005; 38(11):1433–44. https://doi.org/10.1016/j.freeradbiome d.2005.01.019. PMid:15890617.

  • Gilgun SY, Melamed E, Offen D. Oxidative stress induced neurodegenerative diseases: The need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 2001; 40(8):959–75. https://doi. org/10.1016/S0028-3908(01)00019-3.

  • Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev. 2007; 54 (1):34–66. https://doi. org/10.1016/j.brainresrev.2006.11.003. PMid:17222914.

  • Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology. 2008; 55(3):310–18. https://doi.org/10.1016/j.neuropharm.20 08.01.005. PMid:18308346 PMCid:PMC2603601.

  • Mohammadi H et al. Benefit of nanocarrier of magnetic magnesium in rat malathion-induced toxicity and cardiac failure using noninvasive monitoring of electrocardiogram and blood pressure. Toxicol Ind Health. 2011; 27(5):417–29. https://doi. org/10.1177/0748233710387634. PMid:21310777.

  • Barangi S, Hayes AW, Karimi G. The more effective treatment of atrial fibrillation applying the natural compounds; as NADPH oxidase and ion channel inhibitors. Crit Rev Food Sci Nutr. 2018; 58(7):1230–41. https://doi.org/10.1080/10408398.2017.1379000. PMid:28925721.

  • Lakshmi D, et al. Ameliorating effect of fish oil on acrylamide induced oxidative stress and neuronal apoptosis in cerebral cortex. Neurochemical Research. 2012; 37(9):1859–67. https://doi.org/10.1007/s11064- 012-0794-1. PMid:22648048.

  • Zhu YJ, et al. Effects of acrylamide on the nervous tissue antioxidant system and sciatic nerve electrophysiology in the rat. Neurochemical Research. 2008; 33(11):2310. https://doi.org/10.1007/s11064-008-9730-9. PMid:18470611.

  • Xichun Z, Minai Z. Protective role of dark soy sauce against acrylamide induced neurotoxicity in rats by antioxidative activity. Toxicol Mech Methods. 2009; 19:369–74. https://doi.org/10.1080/15376510902806167. PMid:19778214.

  • Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ: Resveratrol ameliorates oxidative DNA damage and protects against acrylamideinduced oxidative stress in rats. Mol Biol Rep. 2012; 39:4589–96. https://doi.org/10.1007/s11033-011-1249- 5. PMid:21947844.

  • Shinomol GK, Raghunath N, Bharath MM, Muralidhara M: Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function. Cent Nerv Syst Agents Med Chem. 2013; 13(1):3–12. https://doi. org/10.2174/1871524911313010003. PMid:23092408.

  • Reagan KE, Wilmarth KR, Friedman M, AbouDonia MB. Acrylamide increases in vitro calcium and calmodulin-dependent kinase-mediated phosp horylation of rat brain and spinal cord neurofilament proteins. Neurochemistry international. 1994; 25(2):133– 43. https://doi.org/10.1016/0197-0186(94)90032-9.

  • Mendilcioglu I, Karaveli S, Erdogan G, Simsek M, et al. Apoptosis and expression of Bcl-2, Bax, p53, caspase-3, and Fas, Fas ligand in placentas complicated by preeclampsia. Clin Exp Obstet Gynecol. 2011; 38:38–42.

  • Xu J, Wang R, Liu J, Qian Q, Li Q, Liu X. Study on DNA damage in L-02 cell induced by acrylamide. Wei sheng yan jiu. Journal of Hygiene Research. 2009; 38(5):589–91.

  • Sumizawa T, Igisu H. Apoptosis induced by acrylamide in SHSY5Y cells. Arch Toxicol. 2007; 81(4):279–82. https:// doi.org/10.1007/s00204-006-0145-6. PMid:16932918.

  • Yang HJ, Lee SH, Jin Y, et al.Toxicological effects of acrylamide on rat testicular gene expression profile. Reprod Toxicol. 2005; 19:527–34. https://doi. org/10.1016/j.reprotox.2004.10.006. PMid:15749267.

  • Li SX, Cui N, Zhang CL, et al. Effect of subchronic exposure to acrylamide induced on the expression of bcl-2, bax and caspase-3 in the rat nervous system. Toxicology. 2006; 217:46–53. https://doi.org/10.1016/j. tox.2005.08.018. PMid:16242231.

  • Sumizawa T, Igisu H. Suppression of acrylamide toxicity by carboxyfullerene in human neuroblastoma cells in vitro. Arch Toxicol. 2009; 83:279–82. https://doi. org/10.1007/s00204-009-0438-7. PMid:19475399.

  • Yilmaz BO, Yildizbayrak N, Aydin Y, et al. Evidence of acrylamide- and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells. Hum Exp Toxicol. 2016; 36(12):1225–35. https://doi. org/10.1177/0960327116686818. PMid:28067054.

  • Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharmaceut Biol. 2011; 49(10):1039–45. https://doi.org/10.3109/1388020 9.2011.563315. PMid:21936628.

  • Sun G, Wang X, Li T, Qu S, Sun J. Taurine attenuates acrylamide-induced apoptosis via a PI3K/AKTdependent manner. Human and Experimental Toxicology. 2018; 37(12):1249–57. https://doi.org/10. 1177/0960327118765335. PMid:29607694.

  • He Y, Tan D, Mi Y, Bai B, Jiang D, et al. Effect of epigallocatechin-3-gallate on acrylamide-induced oxid ative stress and apoptosis in PC12 cells. Human and Experimental Toxicology. 2017; 36(10):1087–99. https:// doi.org/10.1177/0960327116681648. PMid:27920337.

  • Tabeshpour J, Mehri S, Abnous K, Hosseinzadeh H. Neuroprotective effects of thymoquinone in acrylamide-induced peripheral nervous system toxicity through MAPKinase and apoptosis pathways in rat. Neurochem Res. 2019; 44(5):1101–12. https://doi. org/10.1007/s11064-019-02741-4. PMid:30725239.

  • Goudarzi M, Mombeini MA, Fatemi I, Aminzadeh A, et al. Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol Res. 2019; 41(5):419–28. https://doi.org/10.1080/01616412. 2019.1576319. PMid:30735102


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  • Neuroprotective Effect of Naringin on Acrylamideinduced Cytotoxicity in U87MG Cells and Wistar Rats: An in-vitro and in-vivo Study

Abstract Views: 229  |  PDF Views: 1

Authors

Thakur Santhrani.
Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati – 517502, Andhra Pradesh., India
Sathuluri Vineela.
Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur – 522019, Andhra Pradesh., India
Chinta Manga Devi.
Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati – 517502, Andhra Pradesh., India

Abstract


Acrylamide (ACR) is a potent neurotoxic to humans and animals. Neuroprotective effect of naringin was evaluated on ACR induced cytotoxicity using U87MG cells as in-vitro model and rat as in vivo model. ACR (50 mg/kg, i.p.) and Naringin (50 and 100 mg/kg) were administered to rats for 4 weeks. After 4 weeks, rats were sacrificed and sciatic nerves were isolated to determine the biochemical and apoptotic parameters. The exposure of U87MG cells to ACR reduced cell viability. Pretreatment of cells with 5–300 μg/ml naringin before ACR treatment significantly attenuated ACR cytotoxicity in a dose-dependent manner. Naringin down-regulated the Bax and upregulated the Bcl2 protein expression levels and also scavenged ACR induced free radicals in rats. In conclusion, our results indicated that pretreatment with naringin protected cells and rats from ACR-induced cytotoxicity and the neuroprotective effect was due to its antiapoptotic and antioxidant potential.

Keywords


Acrylamide, Apoptosis, Naringin, Neurotoxicity, Oxidative Stress, U87MG Cells.

References





DOI: https://doi.org/10.18311/10.18311%2Fti%2F2021%2Fv28i1%2F26267