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Protective effects of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone against hydrogen peroxide-induced oxidative stress in hepatic L02 cell

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Abstract

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) is a chalcone isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry, and the hepatoprotective effects of DMC on Kunming mice have been studied in previous study. However, the effects of DMC on hepatocyte toxicity and corresponding mechanism remain unclear. The aim of this study was to evaluate the hepatoprotective mechanism of DMC in human hepatocytes (L02) treated with H2O2. The results demonstrated that pretreatment with DMC effectively protected H2O2-induced cell viability loss, cell membrane damage (lactate dehydrogenase, nitric oxide production and caspase-3 accumulation. Besides, DMC pretreatment increased the amount of glutathione, decreased malondialdehyde and the percentage of apoptotic L02 cells compared with only H2O2 treated group. Taken together, these results indicated that DMC had hepatoprotective effects against H2O2-induced liver injury by alleviating oxidative stress and apoptosis process in L02 cells, and DMC might be a potential candidate for the intervention of liver diseases.

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Abbreviations

DMC:

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

ROS:

Reactive oxygen species

GSH:

Reduced glutathione

GSH-PX:

Glutathione peroxidase

GST:

Glutathione-S-transferase

AV:

Annexin V

PI:

Propidineiodide

References

  • Amor, E.C., and I.M. Villasenor. 2005. Spasmolytic flavonoids from Syzygium samarangense (Blume) Merr. & L.M. Perry. Zeitschrift fur Naturforschung C 60: 67–71.

    CAS  Google Scholar 

  • An, R., D. Sohn, G. Jeong, and Y. Kim. 2008. In vitro hepatoprotective compounds from Suaeda glauca. Archives of Pharmacal Research 31: 594–597.

    Article  CAS  PubMed  Google Scholar 

  • Bell, E.F. 1987. History of vitamin E in infant nutrition. The American Journal of Clinical Nutrition 46: 183–186.

    CAS  PubMed  Google Scholar 

  • Budihardjo, I., H. Oliver, and M. Lutter. 1999. Biochemical pathways of caspase activation during apoptosis. Annual Review of Cell and Developmental Biology 15: 269–290.

    Article  CAS  PubMed  Google Scholar 

  • Burton, G.W. 1990. Vitamin E: Antioxidant activity, biokinetics, and bioavailability. Annual Review of Nutrition 10: 357–382.

    Article  CAS  PubMed  Google Scholar 

  • Chen, M., H. Gu, Y. Ye, B. Lin, L. Sun, W. Deng, J. Zhang, and J. Liu. 2010. Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 48: 2980–2987.

    Article  CAS  Google Scholar 

  • Cohen, G.M. 1997. Caspases: the executioners of apoptosis. The Biochemical Journal 326: 1–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cole, K.K., and J.R. Perez-Polo. 2002. Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H2O2 injury. Journal of Neurochemistry 82: 19–29.

    Article  CAS  PubMed  Google Scholar 

  • Coyle, C.H., L.J. Martinez, M.C. Coleman, D.R. Spitz, N.L. Weintraub, and K.N. Kader. 2006. Mechanisms of H2O2-induced oxidative stress in endothelial cells. Free Radical Biology & Medicine 40: 2206–2213.

    Article  CAS  Google Scholar 

  • Das, K., and P. Kar. 2005. Non-alcoholic steatohepatitis. J Assoc Physicians India 53: 50–59.

    Google Scholar 

  • Dung, N.T., J.M. Kim, and S.C. Kang. 2008. Chemical composition, antimicrobial and antioxidant activities of the essential oil and the ethanol extract of Cleistocalyx operculatus (Roxb.) Merr and Perry buds. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 46: 3632–3639.

    Article  CAS  Google Scholar 

  • Englert, R.P., and E. Shacter. 2002. Distinct modes of cell death induced by different reactive oxygen species: amino acyl chloramines mediate hypochlorous acid-induced apoptosis. The Journal of Biological Chemistry 277: 20518–20526.

    Article  CAS  PubMed  Google Scholar 

  • Guevaraa, I., and J. Iwanejkoa. 1998. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clinica Chimica Acta 274: 177–188.

    Article  Google Scholar 

  • Huang, H., J. Niu, L. Zhao, and Y.H. Lu. 2011. Reversal effect of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone on multi-drug resistance in resistant human hepatocellular carcinoma cell line BEL-7402/5-FU. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 18: 1086–1092.

    Article  CAS  Google Scholar 

  • Jaeschke, H. 2000. Reactive oxygen and mechanisms of inflammatory liver injury. Journal of Gastroenterology and Hepatology 15: 718–724.

    Article  CAS  PubMed  Google Scholar 

  • Jia, Z., and H.P. Misra. 2007. Reactive oxygen species in in vitro pesticide-induced neuronal cell (SH-SY5Y) cytotoxicity: Role of NF-κB and caspase-3. Free Radical Biology & Medicine 42: 288–298.

    Article  CAS  Google Scholar 

  • Kang, K.S., I.D. Kim, R.H. Kwon, J.Y. Lee, J.S. Kang, and B.J. Ha. 2008. The effects of fucoidan extracts on CCl(4)-induced liver injury. Archives of Pharmacal Research 31: 622–627.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.J., H. Ko, J. Park, I. Han, E.C. Amor, J. Wha, and H. Ok. 2010. Dimethyl cardamonin inhibits lipopolysaccharide-induced inflammatory factors through blocking NF-κB p65 activation. International Immunopharmacology 10: 1127–1134.

    Article  CAS  PubMed  Google Scholar 

  • Kruman, I.I., and M.P. Mattson. 1999. Pivotal role of mitochondrial calcium uptake in neural cell apoptosis and necrosis. Journal of Neurochemistry 72: 529–540.

    Article  CAS  PubMed  Google Scholar 

  • Lin, F.Y., P.L. Liu, Y.T. Huang, J.H. Chiu, Y.C. Chang, K.M. Man, C.Y. Hong, Y.Y. Ho, M.T. Lai, and Y.H. Chen. 2009. Antioxidative and hepatoprotective effects of acteaminophen on acetaminophen-induced liver damage in rats. Archives of pharmacal research 32: 221–228.

    Article  PubMed  Google Scholar 

  • Loguercio, C., and A. Federico. 2003. Oxidative stress in viral and alcoholic hepatitis. Free Radical Biology & Medicine 34: 1–10.

    Article  CAS  Google Scholar 

  • Manev, H., C.M. Cagnoli, and C. Atabay. 1995. Neuronal apoptosis in an in vitro model of photochemically induced oxidative stress. Experimental Neurology 133: 198–206.

    Article  CAS  PubMed  Google Scholar 

  • Moriya, K., K. Nakagawa, T. Santa, V. Hepatocarcinogenesis, Y. Shintani, H. Fujie, and H. Miyoshi. 2001. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis oxidative stress in the absence of inflammation in a mouse model for hepatitis C. Cancer Research 61: 4365–4370.

    CAS  PubMed  Google Scholar 

  • Qiao, L., J. Yu, P. Dent, and G. Farrell. 2005. NF-κB protects rat ARL-6 hepatocellular carcinoma cells against hydrogen peroxide-induced apoptosis. Cancer Biology & Therapy 4: 1195–1202.

    Article  CAS  Google Scholar 

  • Resurreccion, M.C., I.M. Villasenor, N. Harada, and K. Monde. 2005. Antihyperglycaemic flavonoids from Syzygium samarangense (Blume) Merr. and Perry. Phytotherapy Research 19: 246–251.

    Article  Google Scholar 

  • Samali, A., H. Nordgren, B. Zhivotovsky, E. Peterson, and S. Orrenius. 1999. A comparative study of apoptosis and necrosis in HepG2 cells: oxidant-induced caspase inactivation leads to necrosis. Biochemical and Biophysical Research Communications 255: 6–11.

    Article  CAS  PubMed  Google Scholar 

  • Su, M.Y., H.Y. Huang, L. Li, and Y.H. Lu. 2011. Protective effects of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone to PC12 cells against cytotoxicity induced by hydrogen peroxide. Journal of Agricultural and Food Chemistry 59: 521–527.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi, M., M. Shibata, and E. Niki. 2001. Estimation of lipid peroxidation of live cells using a fluorescent probe, diphenyl-1-pyrenylphosphine. Free Radical Biology & Medicine 31: 164–174.

    Article  CAS  Google Scholar 

  • Traber, M.G., and J.F. Stevens. 2011. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radical Biology and Medicine 51:1000–1013.

    Google Scholar 

  • Tribble, D.L., T.Y. Aw, and D.P. Jones. 1987. The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology 7: 377–386.

    Article  CAS  PubMed  Google Scholar 

  • Valko, M., and D. Leifbritz. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 39: 44–84.

    Article  CAS  Google Scholar 

  • Veigas, J.M., R. Shrivasthava, and B. Neelwarne. 2008. Efficient amelioration of carbon tetrachloride induced toxicity in isolated rat hepatocytes by Syzygium cumini Skeels extract. Toxicology In Vitro 22: 1440–1446.

    Article  CAS  PubMed  Google Scholar 

  • Weng, D., Y. Lu, Y. Wei, Y. Liu, and P. Shen. 2007. The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice. Toxicology 232: 15–23.

    Article  CAS  PubMed  Google Scholar 

  • Ye, C.L., J.W. Liu, D.Z. Wei, Y.H. Lu, and F. Qian. 2005. In vivo antitumor activity by 2′4′-dihydroxy-6′-methoxy-3′5′-dimethylchalcone in a solid human carcinoma xenograft model. Cancer Chemotherapy and Pharmacology 55: 447–452.

    Article  CAS  PubMed  Google Scholar 

  • Ye, C.L., Y.H. Lu, and D.Z. Wei. 2004a. Flavonoids from Cleistocalyx operculatus. Phytochemistry 65: 445–447.

    Article  CAS  PubMed  Google Scholar 

  • Ye, C.L., J.W. Liu, D.Z. Wei, Y.H. Lu, and F. Qian. 2004b. In vitro anti-tumor activity of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone against six established human cancer cell lines. Pharmacological Research 50: 505–510.

    Article  CAS  PubMed  Google Scholar 

  • Yu, W.G., J. Qian, and Y.H. Lu. 2011. Hepatoprotective effects of 2′, 4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone on CCl4-induced acute liver injury in mice. Journal of Agricultural and Food Chemistry 59: 12821–12829.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by “the Fundamental Research Funds for the Central Universities”, and partially supported by the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), Shanghai Leading Academic Discipline Project (B505), and the 863 Project (2011AA090702).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Yue Lu, Ying-Chun Hu & Yan-Hua Lu

  2. College of Tourism and Food Science, Shanghai Business School, Shanghai, 200235, People’s Republic of China

    Yan-Yan Zhang

  3. Unilever R&D Shanghai, 5/F, 66 Linxin Road, Shanghai, 200335, People’s Republic of China

    Ying-Chun Hu

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  1. Yue Lu
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Correspondence to Yan-Hua Lu.

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Lu, Y., Zhang, YY., Hu, YC. et al. Protective effects of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone against hydrogen peroxide-induced oxidative stress in hepatic L02 cell. Arch. Pharm. Res. 37, 1211–1218 (2014). https://doi.org/10.1007/s12272-014-0334-4

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