Food Science and Preservation (한국식품저장유통학회지)

The Korean Society of Food Preservation (한국식품저장유통학회)
권호 표지
DOI QR코드

DOI QR Code

Efficacy of Elaeagnus umbellata leaves on prevention of cadmium-induced toxicity in HepG2 cells

  • Jae-Yeul Lee (Institute of Natural Science, Keimyung University) ;
  • Seun-Ah Yang (Department of Food Science and Technology, Keimyung University) ;
  • Won-Bin Bae (Department of Food Science and Technology, Keimyung University)
  • Received : 2023.08.16
  • Accepted : 2023.09.29
  • Published : 2023.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A3055952).

References

  1. Abdelrazek HM, Helmy SA, Elsayed DH, Ebaid HM, Mohamed RM. Ameliorating effects of green tea extract on cadmium induced reproductive injury in male wistar rats with respect to androgen receptors and caspase-3. Reprod Biol, 16, 300-308 (2016)
  2. Abri A, Maleki M. Isolation and identification of gallic acid from the elaeagnus angustifolia leaves and determination of total phenolic, flavonoids contents and investigation of antioxidant activity. Iran Chem Commun, 4, 146-154 (2016)
  3. Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells. Onco Targets Ther, 75-84 (2013)
  4. Aronis A, Melendez J, Golan O, Shilo S, Dicter N, Tirosh O. Potentiation of fas-mediated apoptosis by attenuated production of mitochondriaderived reactive oxygen species. Cell Death Differ, 10, 335-344 (2003)
  5. Athmouni K, Belhaj D, El Feki A, Ayadi H. Optimization, antioxidant properties and GCMS analysis of Periploca angustifolia polysaccharides and chelation therapy on cadmium-induced toxicity in human HepG2 cells line and rat liver. Int J Biol Macromol, 108, 853-862 (2018) https://doi.org/10.1016/j.ijbiomac.2017.10.175
  6. Aydin HH, Celik HA, Deveci R, Terzioglu E, Karacali S, Mete N, Akarca U, Batur Y. Characterization of the cellular response during apoptosis induction in cadmium-treated hep g2 human hepatoma cells. Biol Trace Elem Res, 95, 139-153 (2003) https://doi.org/10.1385/BTER:95:2:139
  7. Devi KP, Malar DS, Nabavi SF, Sureda A, Xiao J, Nabavi SM, Daglia M. Kaempferol and inflammation: From chemistry to medicine. Pharmacol Res, 99, 1-10 (2015) https://doi.org/10.1016/j.phrs.2015.05.002
  8. Escobar MDC, Souza V, Bucio L, Hernandez E, Gomez-Quiroz LE, Ruiz MCG. Mapk activation is involved in cadmium-induced hsp70 expression in hepg2 cells. Toxicol Mech Methods, 19, 503-509 (2009) https://doi.org/10.3109/15376510903325670
  9. Fatur T, Tusek M, Falnoga I, Scancar J, Lah T, Filipic M. DNA damage and metallothionein synthesis in human hepatoma cells (hepg2) exposed to cadmium. Food Chem Toxicol, 40, 1069-1076
  10. Fotakis G, Cemeli E, Anderson D, Timbrell JA. Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line. Toxicol in Vitro, 19, 481-489 (2005) https://doi.org/10.1016/j.tiv.2005.02.001
  11. Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A. The effects of cadmium toxicity. Int J Environ Res Public Health, 17, 3782 (2020)
  12. Habeebu SSM, Liu J, Klaassen CD. Cadmiuminduced apoptosis in mouse liver. Toxicol Appl Pharmacol, 149, 203-209 (1998)
  13. He X, Chen MG, Ma Q. Activation of Nrf2 in defense against cadmium-induced oxidative stress. Chem Res Toxicol, 21, 1375-1383 (2008) https://doi.org/10.1021/tx800019a
  14. Hsiao CJJ, Stapleton SR. Characterization of cdinduced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein jnk and transcription factor ap-1. J Biochem Mol Toxicol, 18, 133-142 (2004). https://doi.org/10.1002/jbt.20018
  15. Jadeja RN, Upadhyay KK, Devkar RV, Khurana S. Naturally occurring Nrf2 activators: Potential in treatment of liver injury. Oxid Med Cell Longev, 2016, 3453926 (2016)
  16. Kang HR, Jung JK, Park SH, Lee JY, Yang SA. Anti-oxidant, anti-inflammatory, and antibacterial effects of extracts from Elaeagnus umbellata leaves obtained using different extract conditions. Korean J Food Preserv, 27, 374-384 (2020) https://doi.org/10.11002/kjfp.2020.27.3.374
  17. Kang MS, Oh JS, Kang IC, Hong SJ, Choi CH. Inhibitory effect of methyl gallate and gallic acid on oral bacteria. J Microbiol, 46, 744-750 (2008) https://doi.org/10.1007/s12275-008-0235-7
  18. Kim MJ, Lim JS, Yang SA. Component analysis and anti-proliferative effects of ethanol extracts of fruits, leaves, and stems from Elaeagnus umbellata in HepG2 cells. J Korean Soc Food Sci Nutr, 45, 828-834 (2016) https://doi.org/10.3746/jkfn.2016.45.6.828
  19. Kim SH, Jun CD, Suk K, Choi BJ, Lim H, Park S, Lee SH, Shin HY, Kim DK, Shin TY. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol Sci, 91, 123-131 (2006) https://doi.org/10.1093/toxsci/kfj063
  20. Kroes BV, Van Den Berg A, Van Ufford HQ, Van Dijk H, Labadie R. Anti-inflammatory activity of gallic acid. Planta Med, 58, 499-504 (1992) https://doi.org/10.1055/s-2006-961535
  21. Lawal AO, Marnewick JL, Ellis EM. Heme oxygenase-1 attenuates cadmium-induced mitochondrial-caspase 3-dependent apoptosis in human hepatoma cell line. BMC Pharmacol Toxicol, 16, 1-13 (2015) https://doi.org/10.1186/2050-6511-16-1
  22. Lee CH, Bae JY, Park JH. Pharmacognostical studies on the Korean folk medicine 'borisunamu'. Korean J Pharmacogn, 42, 1-5 (2011)
  23. Lee SE, Yang H, Jeong SI, Jin YH, Park CS, Park YS. Induction of heme oxygenase-1 inhibits cell death in crotonaldehyde-stimulated hepg2 cells via the pkc-δ-p38 -Nrf2 pathway. PLOS ONE, 7, e41676 (2012)
  24. Martin MA, Ramos S, Mateos R, Granado Serrano ABN, Izquierdo-Pulido MA, Bravo L, Goya L. Protection of human hepg2 cells against oxidative stress by cocoa phenolic extract. J Agric Food Chem, 56, 7765-7772 (2008) https://doi.org/10.1021/jf801744r
  25. Matovic V, Buha A, Dukic-Cosic D, Bulat Z. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol, 78, 130-140 (2015) https://doi.org/10.1016/j.fct.2015.02.011
  26. Mattie MD, Freedman JH. Protective effects of aspirin and vitamin E (α-tocopherol) against copper- and cadmium-induced toxicity. Biochem Biophys Res Commun, 285, 921-925 (2001) https://doi.org/10.1006/bbrc.2001.5259
  27. Oh SH, Choi JE, Lim SC. Protection of betulin against cadmium-induced apoptosis in hepatoma cells. Toxicol, 220, 1-12 (2006) https://doi.org/10.1016/j.tox.2005.08.025
  28. Oh SH, Lim SC. A rapid and transient ros generation by cadmium triggers apoptosis via caspase-dependent pathway in hepg2 cells and this is inhibited through n-acetylcysteine-mediated catalase upregulation. Toxicol Appl Pharmacol, 212, 212-223 (2006) https://doi.org/10.1016/j.taap.2005.07.018
  29. Ohno Y, Fukuda K, Takemura G, Toyota M, Watanabe M, Yasuda N, Xinbin Q, Maruyama R, Akao S, Gotou K, Fujiwara T, Fujiwara H. Induction of apoptosis by gallic acid in lung cancer cells. Anti-Cancer Drugs, 10, 845-852 (1999) https://doi.org/10.1097/00001813-199910000-00008
  30. Papaiahgari S, Kleeberger SR, Cho HY, Kalvakolanu DV, Reddy SP. Nadph oxidase and ERK signaling regulates hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells. J Biol Chem, 279, 42302-42312 (2004) https://doi.org/10.1074/jbc.M408275200
  31. Park SH, Jhee KH, Yang SA. Protective effects of an ethanol extract of Elaeagnus umbellata leaves on α-msh-induced melanin production in b16-f0 cells and uvb-induced damage in ccd-986sk cells. J Life Sci, 29, 555-563 (2019)
  32. Park SJ, Lee JR, Jo MJ, Park SM, Ku SK, Kim SC. Protective effects of Korean red ginseng extract on cadmium-induced hepatic toxicity in rats. J Ginseng Res, 37, 37-44 (2013) https://doi.org/10.5142/jgr.2013.37.37
  33. Poliandri AH, Cabilla JP, Velardez MO, Bodo CC, Duvilanski BH. Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants. Toxicol Appl Pharmacol, 190, 17-24 (2003)
  34. Pourahmad J, Obrien PJ. A comparison of hepatocyte cytotoxic mechanisms for cu2+ and cd2+. Toxicol, 143, 263-273 (2000) https://doi.org/10.1016/S0300-483X(99)00178-X
  35. Rafique N, Khan T, Shah AJ. Calcium entry blocking activity of the Elaeagnus umbellata fruit extract explains its use in diarrhea and gut spasm. Bangladesh J Pharmacol, 11, 585-592 (2016) https://doi.org/10.3329/bjp.v11i3.26101
  36. Seo JY, Lee YJ, Oh MH, Lee SH. In vitro nasal epithelial toxicity by cadmium accompanies up-regulation of runx3 protein with activation of pi3-kinase/akt. Mol Cell Toxicol, 9, 159-167 (2013) https://doi.org/10.1007/s13273-013-0020-5
  37. Sharma V, Joseph C, Ghosh S, Agarwal A, Mishra MK, Sen E. Kaempferol induces apoptosis in glioblastoma cells through oxidative stress. Mol Cancer Ther, 6, 2544-2553 (2007) https://doi.org/10.1158/1535-7163.MCT-06-0788
  38. Shen G, Hebbar V, Nair S, Xu C, Li W, Lin W, Keum YS, Han J, Gallo MA, Kong A-NT. Regulation of Nrf2 transactivation domain activity: The differential effects of mitogen-activated protein kinase cascades and synergistic stimulatory effect of raf and creb-binding protein. J Biol Chem, 279, 23052-23060 (2004)
  39. Shimoda R, Nagamine T, Takagi H, Mori M, Waalkes MP. Induction of apoptosis in cells by cadmium: Quantitative negative correlation between basal or induced metallothionein concentration and apoptotic rate. Toxicol Sci, 64, 208-215 (2001) https://doi.org/10.1093/toxsci/64.2.208
  40. Tsai JS, Chao CH, Lin LY. Cadmium activates multiple signaling pathways that coordinately stimulate akt activity to enhance c-myc mrna stability. PLoS One, 11, e0147011 (2016)
  41. Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Hereti RI, Alexandropoulou KN, Basayannis AC, Mykoniatis MG. Time-course of cadmium-induced acute hepatotoxicity in the rat liver: The role of apoptosis. Arch Toxicol, 77, 694-701 (2003) https://doi.org/10.1007/s00204-003-0499-y
  42. Urani C, Melchioretto P, Canevali C, Morazzoni F, Gribaldo L. Metallothionein and hsp70 expression in hepg2 cells after prolonged cadmium exposure. Toxicol in Vitro, 21, 314-319 (2007) https://doi.org/10.1016/j.tiv.2006.08.014
  43. Wang T, Hou Y, Hu H, Wang C, Zhang W, Li H, Cheng Z, Yang L. Functional validation of phytoene synthase and lycopene ε-cyclase genes for high lycopene content in autumn olive fruit (Elaeagnus umbellata ). J Agric Food Chem, 68, 11503-11511 (2020) https://doi.org/10.1021/acs.jafc.0c03092
  44. Yari A, Sarveazad A, Asadi E, Raouf Sarshoori J, Babahajian A, Amini N, Amidi F, Bahadoran H, Joghataei M, Asadi M. Efficacy of crocus sativus l. On reduction of cadmium-induced toxicity on spermatogenesis in adult rats. Andrologia, 48, 1244-1252 (2016) https://doi.org/10.1111/and.12568
  45. Yen GC, Duh PD, Tsai HL. Antioxidant and prooxidant properties of ascorbic acid and gallic acid. Food Chem, 79, 307-313 (2002) https://doi.org/10.1016/S0308-8146(02)00145-0
  46. Yoon KY, Hong JY, Shin SR. Analysis on the components of the Elaeagnus multiflora thunb. Leaves. Korean J Food Preserv, 14, 639-644 (2007)
  47. Zhang B, Yu D, Luo N, Yang C, Zhu Y. Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1 signaling pathway. Korean J Physiol Pharmacol, 24, 373-384 (2020) https://doi.org/10.4196/kjpp.2020.24.5.373