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

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Authors

  • Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur, 522019, Andhra Pradesh ,IN
  • Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati, 517502, Andhra Pradesh ,IN
  • Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupati, 517502, Andhra Pradesh ,IN

DOI:

https://doi.org/10.18311/ti/2021/v28i1/26267

Keywords:

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

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 & 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 signiï¬cantly attenuated ACR cytotoxicity in a dose-dependent manner. Naringin down-regulated the Bax and up-regulated 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.

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Published

2021-03-24

How to Cite

Vineela, S., Manga Devi, C., & Santhrani, T. (2021). Neuroprotective Effect of Naringin on Acrylamideinduced Cytotoxicity in U87MG Cells and Wistar Rats: An <i>in-vitro</i> and <i>in-vivo</i> Study. Toxicology International, 28(1), 49–56. https://doi.org/10.18311/ti/2021/v28i1/26267

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Section

Original Research
Received 2020-10-17
Accepted 2021-01-18
Published 2021-03-24

 

References

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 DOI: https://doi.org/10.1093/toxsci/kfg165

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 DOI: 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 DOI: 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. DOI: https://doi.org/10.1007/0-387-24980-X_2

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 DOI: https://doi.org/10.1080/10408440600851377

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 DOI: 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 DOI: https://doi.org/10.1371/journal.pone.0143868

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 DOI: https://doi.org/10.1016/j.yebeh.2014.09.058

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 DOI: https://doi.org/10.1016/j.intimp.2012.04.019

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 DOI: https://doi.org/10.1016/j.fct.2012.07.033

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. c lnu. 2004. 01. 006. PMid:15380892 DOI: https://doi.org/10.1016/j.clnu.2004.01.006

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 DOI: https://doi.org/10.1016/j.neuint.2011.08.022

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 DOI: 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 DOI: 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 DOI: https://doi.org/10.1016/0003-9861(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 DOI: 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 DOI: 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 DOI: https://doi.org/10.1007/s10571-011-9752-8

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/10.1080/01480545.2017.1381108. PMid:29072525 DOI: https://doi.org/10.1080/01480545.2017.1381108

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/10.1080/01480545.2018.1536140. PMid:30574809 DOI: https://doi.org/10.1080/01480545.2018.1536140

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 DOI: https://doi.org/10.1016/j.freeradbiomed.2005.01.019

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 DOI: 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 DOI: https://doi.org/10.1016/j.brainresrev.2006.11.003

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 DOI: https://doi.org/10.1016/j.neuropharm.2008.01.005

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 DOI: https://doi.org/10.1177/0748233710387634

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 DOI: https://doi.org/10.1080/10408398.2017.1379000

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 DOI: https://doi.org/10.1007/s11064-012-0794-1

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 DOI: https://doi.org/10.1007/s11064-008-9730-9

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 DOI: https://doi.org/10.1080/15376510902806167

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 DOI: https://doi.org/10.1007/s11033-011-1249-5

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 DOI: https://doi.org/10.2174/1871524911313010003

Reagan KE, Wilmarth KR, Friedman M, Abou- Donia 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 DOI: 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 DOI: https://doi.org/10.1007/s00204-006-0145-6

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 DOI: https://doi.org/10.1016/j.reprotox.2004.10.006

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 DOI: https://doi.org/10.1016/j.tox.2005.08.018

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 DOI: https://doi.org/10.1007/s00204-009-0438-7

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 DOI: https://doi.org/10.1177/0960327116686818

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/10.3109/13880209.2011.563315. PMid:21936628 DOI: https://doi.org/10.3109/13880209.2011.563315

Sun G, Wang X, Li T, Qu S, Sun J. Taurine attenuates acrylamide-induced apoptosis via a PI3K/AKT dependent manner. Human and Experimental Toxicology. 2018; 37(12):1249–57. https://doi.org/10.1177/0960327118765335. PMid:29607694 DOI: https://doi.org/10.1177/0960327118765335

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

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 DOI: https://doi.org/10.1007/s11064-019-02741-4

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 DOI: https://doi.org/10.1080/01616412.2019.1576319