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Ferulic acid renders protection to HEK293 cells against oxidative damage and apoptosis induced by hydrogen peroxide

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Abstract

The application of antioxidants has been considered as an important and effective approach against conditions in which oxidative stress occurs. Especially, ferulic acid (FA) is an important antioxidant which exerts potency against cellular damage in the presence of oxidants. In the current study, the resistance effect of FA on hydrogen peroxide (H2O2)-stressed human embryonic kidney 293 cells (HEK293) in vitro was investigated. FA (1 mM) increased HEK293 cells’ viability and significantly reduced H2O2-induced cellular apoptosis, which was confirmed with flow cytometry and morphological results. Cell cycle analysis indicated low percentage of sub-G0 population of FA-treated HEK293 cells that confirmed its resistance effect. The FA-treated HEK293 cells followed by H2O2 exposure resulted in decreased ROS levels compared to control (H2O2-treated only). The results indicated that pretreatment of FA on cell prior to H2O2 exposure could significantly improve cell survival and increase catalase (CAT) and superoxide dismutase (SOD) levels. On the other hand, reduction in the levels of MDA and ROS was obvious. It can be concluded that FA may protect HEK293 cells from injury induced by H2O2 through regulation of intracellular antioxidant enzyme activities and cell cycle distribution. The reduction in mitochondrial membrane potential was also inhibited by FA treatment. These results suggested the importance of naturally occurring antioxidants such as FA in therapeutic intervention methodology against oxidative stress-related diseases.

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References

  • Almaliti J, Nada SE, Carter B, Shah ZA, Tillekeratne L (2013) Natural products inspired synthesis of neuroprotective agents against H2O2-induced cell death. Bioorg Med Chem Lett 23:1232–1237

    Article  CAS  PubMed  Google Scholar 

  • Bandugula VR, Prasad RN (2013) 2-Deoxy-d-glucose and ferulic acid modulates radiation response signaling in non-small cell lung cancer cells. Tumor Biol 34:251–259

    Article  CAS  Google Scholar 

  • Bhattacharjee S, Deterding LJ, Chatterjee S, Jiang J, Ehrenshaft M, Lardinois O, Ramirez DC, Tomer KB, Mason RP (2011) Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS. Free Radic Biol Med 50:1536–1545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Calabrese V, Calafato S, Puleo E, Cornelius C, Sapienza M, Morganti P, Mancuso C (2008) Redox regulation of cellular stress response by ferulic acid ethyl ester in human dermal fibroblasts: role of vitagenes. Clin Dermatol 26:358–363

    Article  PubMed  Google Scholar 

  • Cao W, Li X, Wang X, Fan H, Zhang X, Hou Y, Liu S, Mei Q (2010) A novel polysaccharide, isolated from Angelica sinensis (Oliv.) Diels induces the apoptosis of cervical cancer HeLa cells through an intrinsic apoptotic pathway. Phytomedicine 17:598–605

    Article  CAS  PubMed  Google Scholar 

  • Cheng CY, Ho TY, Lee EJ, Su SY, Tang NY, Hsieh CL (2008) Ferulic acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats. The American journal of Chinese medicine 36:1105–1119

    Article  CAS  PubMed  Google Scholar 

  • DeFeudis FV, Papadopoulos V, Drieu K (2003) Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol 17:405–417

    Article  CAS  PubMed  Google Scholar 

  • Devasagayam T, Tilak J, Boloor K, Sane K, Ghaskadbi S, Lele R (2004) Free radicals and antioxidants in human health: current status and future prospects. Japi 52:794–804

    CAS  PubMed  Google Scholar 

  • Dong C, Eldawud R, Sargent LM, Kashon ML, Lowry D, Rojanasakul Y, Dinu CZ (2014) Towards elucidating the effects of purified MWCNTs on human lung epithelial cells. Environ Sci: Nano 1:595–603

    CAS  Google Scholar 

  • Gao Y, Zhang HW, Qiao HL, Wang W, Chang JB (2010) Protective effect of 3-butyl-6-bromo-1 (3H)-isobenzofuranone on hydrogen peroxide-induced damage in PC12 cells. Brain Res 1358:239–247

    Article  CAS  PubMed  Google Scholar 

  • Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci 73:2424–2428

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge J (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Higuchi K, Mitsuhashi N, J-i S, Maebayashi K, Sakurai H, Akimoto T, Niibe H (2000) Caffeine enhanced radiosensitivity of rat tumor cells with a mutant-type p53 by inducing apoptosis in a p53-independent manner. Cancer Lett 152:157–162

    Article  CAS  PubMed  Google Scholar 

  • Hou YZ, Yang J, Zhao GR, Yuan YJ (2004) Ferulic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II. Eur J Pharmacol 499:85–90

    Article  CAS  PubMed  Google Scholar 

  • Huang SH, Lin CM, Chiang BH (2008) Protective effects of Angelica sinensis extract on amyloid β-peptide-induced neurotoxicity. Phytomedicine 15:710–721

    Article  CAS  PubMed  Google Scholar 

  • Kanski J, Aksenova M, Stoyanova A, Butterfield DA (2002) Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. J Nutr Biochem 13:273–281

    Article  CAS  PubMed  Google Scholar 

  • Koh PO (2013) Ferulic acid prevents cerebral ischemic injury-induced reduction of hippocalcin expression. Synapse 67:390–398

    Article  CAS  PubMed  Google Scholar 

  • Leichert LI, Gehrke F, Gudiseva HV, Blackwell T, Ilbert M, Walker AK, Strahler JR, Andrews PC, Jakob U (2008) Quantifying changes in the thiol redox proteome upon oxidative stress in vivo. Proc Natl Acad Sci 105:8197–8202

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA, Herman B (1998) The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Bba-Bioenergetics 1366:177–196

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN (2002) Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proc Natl Acad Sci 99:2356–2361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lü JM, Lin PH, Yao Q, Chen C (2010) Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 14:840–860

    Article  PubMed Central  PubMed  Google Scholar 

  • Lu YH, Su MY, Huang HY, Lin L, Yuan CG (2010) Protective effects of the citrus flavanones to PC12 cells against cytotoxicity induced by hydrogen peroxide. Neurosci Lett 484:6–11

    Article  CAS  PubMed  Google Scholar 

  • Manchanda PK, Jones GN, Lee AA, Pringle DR, Zhang M, Yu L, La Perle KM, Kirschner LS (2013) Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors. Oncogene 32:3491–3499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Manke A, Luanpitpong S, Dong C, Wang L, He X, Battelli L, Derk R, Stueckle TA, Porter DW, Sager T, Gou H, Dinu CZ, Wu N, Mercer RR, Rojanasakul Y (2014) Effect of fiber length on carbon nanotube-induced fibrogenesis. Int J Mol Sci 15:7444–7461

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  • Ou S, Kwok KC (2004) Ferulic acid: pharmaceutical functions, preparation and applications in foods. J Sci Food Agric 84:1261–1269

    Article  CAS  Google Scholar 

  • Panneerselvam L, Subbiah K, Arumugam A, Senapathy JG (2013) Ferulic acid modulates fluoride-induced oxidative hepatotoxicity in male Wistar rats. Biol Trace Elem Res 151:85–91

    Article  CAS  PubMed  Google Scholar 

  • Qi F, Li A, Lv H, Zhao L, Li J, Gao B, Tang W (2008) Apoptosis-inducing effect of cinobufacini, Bufo bufo gargarizans cantor skin extract, on human hepatoma cell line BEL-7402. Drug Discov Ther 2:339

    CAS  PubMed  Google Scholar 

  • Rinaldi P, Polidori M, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P (2003) Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 24:915–919

    Article  CAS  PubMed  Google Scholar 

  • Schroeder BR, Ghare MI, Bhattacharya C, Paul R, Yu Z, Zaleski PA, Bozeman TC, Rishel MJ, Hecht SM (2014) The disaccharide moiety of bleomycin facilitates uptake by cancer cells. J Am Chem Soc 136:13641–13656

    Article  CAS  PubMed  Google Scholar 

  • Shanthakumar J, Karthikeyan A, Bandugula VR, Prasad NR (2012) Ferulic acid, a dietary phenolic acid, modulates radiation effects in Swiss albino mice. Eur J Pharmacol 691:268–274

    Article  CAS  PubMed  Google Scholar 

  • Si J, Zhang H, Wang Z, Wu Z, Lu J, Di C, Zhou X, Wang X (2013) Effects of 12C6+ ion radiation and ferulic acid on the zebrafish (Danio rerio) embryonic oxidative stress response and gene expression. Mutat Res 745–746:26–33

    Article  PubMed  Google Scholar 

  • Siegrist KJ, Reynolds SH, Kashon ML, Lowry DT, Dong C, Hubbs AF, Young SH, Salisbury JL, Porter DW, Benkovic SA, McCawley M, Keane MJ, Mastovich JT, Bunker KL, Cena LG, Sparrow MC, Sturgeon JL, Dinu CZ, Sargent LM (2014) Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses. Part Fibre Toxicol 11:6

    Article  PubMed Central  PubMed  Google Scholar 

  • Srinivasan M, Sudheer AR, Menon VP (2007) Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr 40:92

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang BH, Ou Yang JP (2005) Pharmacological actions of sodium ferulate in cardiovascular system. Cardiovasc Drug Rev 23:161–172

    Article  PubMed  Google Scholar 

  • Xu ZL, Gao H, Ou-Yang KQ, Cai SX, Hu YH (2004) Establishment of a cell-based assay to screen regulators for Klotho gene promoter. Acta Pharmacol Sin 25:1165–1170

    CAS  PubMed  Google Scholar 

  • Zhang M, Manchanda PK, Wu D, Wang Q, Kirschner LS (2014) Knockdown of PRKAR1A, the gene responsible for Carney complex, interferes with differentiation in osteoblastic cells. Mol Endocrinol 28:295–307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhu KX, Guo X, Guo XN, Peng W, Zhou HM (2013) Protective effects of wheat germ protein isolate hydrolysates (WGPIH) against hydrogen peroxide-induced oxidative stress in PC12 cells. Food Res Int 53:297–303

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was sponsored by Qing Lan Project China Postdoctoral Science Foundation (Grant No. 2014M560396), Jiangsu Planned Projects for Postdoctoral Research Funds (Grant No. 1402072C), and the National Key Technology R&D Program (Grant No. 2013AA102201).

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Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, Jiangsu Province, People’s Republic of China

    Yuan-Yuan Bian, Jia Guo, Hamid Majeed, Ke-Xue Zhu, Xiao-Na Guo, Wei Peng & Hui-Ming Zhou

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  1. Yuan-Yuan Bian
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  2. Jia Guo
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  3. Hamid Majeed
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  4. Ke-Xue Zhu
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  5. Xiao-Na Guo
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  6. Wei Peng
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  7. Hui-Ming Zhou
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Correspondence to Ke-Xue Zhu or Hui-Ming Zhou.

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Editor: T. Okamoto

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Bian, YY., Guo, J., Majeed, H. et al. Ferulic acid renders protection to HEK293 cells against oxidative damage and apoptosis induced by hydrogen peroxide. In Vitro Cell.Dev.Biol.-Animal 51, 722–729 (2015). https://doi.org/10.1007/s11626-015-9876-0

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  • DOI: https://doi.org/10.1007/s11626-015-9876-0

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