槲皮素和茶多酚抑制VO(acac)2导致的线粒体损伤和细胞毒性

摘要/Abstract

摘要：

近年来, 钒化合物的降血糖和抗癌作用受到人们的关注。但是钒金属毒性成为限制其进一步药物开发的重要问题。但是越来越多的研究指出钒化合物的毒性与其诱导氧化应激相关。由于槲皮素和茶多酚对于很多氧化应激相关疾病有一定的预防作用, 本文主要在分离的线粒体层次研究槲皮素和茶多酚抑制乙酰丙酮氧钒(VO(acac)2)引起毒性, 进而对线粒体产生的保护作用。实验结果表明, 槲皮素/茶多酚可以显著地抑制由VO(acac)2引起的线粒体毒性和细胞毒性, 如线粒体肿胀、线粒体膜电位耗散、线粒体ROS过度释放以及细胞活力下降。实验结果对于如何通过天然抗氧化剂在保留钒化合物的药效的同时去除钒化合物的毒性、在药物设计上构建更合理的钒化合物药物具有意义。

关键词: 槲皮素, 茶多酚, VO(acac)2, 线粒体

Abstract:

Vanadium compounds are promising therapeutic agents for the treatment of diabetes and cancer. However, vanadium toxicity has been a great concern. Many works suggested that vanadium-induced oxidative stress is a major reason of vanadium toxicity. Quercetin and green tea polyphenols (GTP) are well-known antioxidants that play important roles in the prevention of many oxidative stress-related diseases. In this study, we investigated the protective effects of quercetin and GTP against damages caused by VO(acac)2 on isolated mitochondria and whole cells. The experimental results demonstrated that quercetin and GTP could significantly inhibit mitochondrial dysfunctions induced by VO(acac)2, such as mitochondrial swelling, depolarization of the inner mitochondrial membrane potential (Δψm), and increased release of reactive oxygen species (ROS). Moreover, they also reduce cytotoxicity in Hep G2 cells. These results indicated that use of natural antioxidants to control the metal toxicity of vanadium compounds may be a promising strategy for developing metal-based therapeutic agents.

Key words: VO(acac)2, VO(acac)2, Quercetin and green tea polyphenols, Quercetin and green tea polyphenols, Mitochondria, Mitochondria

中图分类号:

R962.1

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 20671008).
^*Corresponding author. Tel.: 86-10-82801539; fax: 86-10-62015584;
e-mail: ^**xyang@bjmu.edu.cn; ^*Huixue Liu, hphx@sina.com

赵月斌, 施喆, 叶丽华, 刘会雪^*, 杨晓达^*, 王夔.

槲皮素和茶多酚抑制VO(acac)₂导致的线粒体损伤和细胞毒性

[J]. .

Yue-Bin Zhao, Zhe Shi, Li-Hua Ye, Hui-Xue Liu^*, Xiao-Da Yang^*, Kui Wang. Quercetin and green tea polyphenols inhibit the mitochondrial damages and cytotoxicity induced by VO(acac)₂[J]. .

参考文献

[1] Thompson, K.H.; Orvig, C. J. Inorg. Biochem. 2006, 100, 1925-1935.
[2] Srivastava, A.K.; Mehdi, M.Z. Diabetic. Med. 2005, 22, 2-13.
[3] Crans, D.C.; Smee, J.J.; Gaidamauskas, E.; Yang, L. Chem. Rev. 2004, 104, 849-902.
[4] Evangelou, A.M. Crit. Rev. Oncol. Hematol. 2002, 42, 249-265.
[5] Fu,Y.; Wang, Q; Yang, X.G.; Yang, X.D.; Wang, K. J. Biol. Inorg. Chem. 2008, 13, 1001-1009.
[6] Oster, M.H.; Llobet, J.M.; Domingo, J.L.; German, J.B. Toxicology. 1993, 83, 115-130.
[7] Cohen, N.; Halberstam, M.; Shlimovich, P.; Chang, C.J.; Shamoon, H.; Rossetti, L. J. Clin. Invest. 1995, 95, 2501-2509.
[8] Zhang, Y.; Yang, X.D.; Wang, K.; Crans, D.C. J. Inorg. Biochem. 2006, 100, 80-87.
[9] Zhang, S.Q.; Chen, G.H.; Lu, W.L.; Zhang, Q. J. Bone. Miner. Metab. 2007, 25, 293-301.
[10] Soares, S.S.; Martins, H.; Duarte, R.O.; Moura, J.J.G.; Coucelo, J.; Gutiérrez-Merino, C.; Aureliano, M. J. Inorg. Biochem. 2007, 101, 80-88.
[11] Soares, S.S.; Gutiérrez-Merino, C.; Aureliano, M. Toxi-cology. 2007, 83, 1-9.
[12] Soares, S.S.; Gutiérrez-Merino, C.; Aureliano, M. J. Inorg. Biochem. 2007, 101, 789-796.
[13] Soares, S.S.; Martins, H.; Gutiérrez-Merino, C.; Aureliano, M. Comp. Biochem. Physiol. Part C. 2008, 147, 168-178.
[14] Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Biochim. Biophys. Acta. Bioenerg. 2006, 1757, 509-517.
[15] Andreyev, A.Y.; Kushnareva, Y.E.; Starkov, A.A. Biochemistry (Mosc). 2005, 70, 200-214.
[16] Yang, X.G.; Yang, X.D.; Yuan, L.; Wang, K.; Crans, D.C. Pharm. Res. 2004, 21, 1026-1033.
[17] Willsky, G.R.; Chi, L.H.; Liang,Y.; Gaile, D.P.; Hu, Z.; Crans, D.C. Physiol. Genomics. 2006, 10, 196-205.
[18] Huang, C.; Ding, M.; Li, J.; Leonard, S.S.; Rojanasakul, Y.; Castranova,V.; Vallyathan, V.; Ju, G.; Shi, X.L. J. Biol. Chem. 2001, 276, 22397-22403.
[19] Huang, Y.C.T.; Soukup, J.; Harder, S.; Becker, S. Am. J. Physiol. Cell Physiol. 2003, 284, 24-32.
[20] Middleton, E.; Kandaswami, C.; Theoharides, T.C. Pharm. Rev. 2000, 52, 673-751.
[21] Arts, I.C.W.; Hollman, P.C.H. Am. J. Clin. Nutr. 2005, 81, 317-325.
[22] Cabrera, C.; Artacho, R.; Gimenez, R. J. Am. Coll. Nutr. 2006, 25, 79-99.
[23] Geetha, T.; Malhotra, V.; Chopra, K.; Indupal, K. Indian. J. Exp. Biol. 2005, 43, 61-67.
[24] Winn, R.N.; Kling, H.; Norris, M.B. Environ. Mol. Mutagen. 2005, 46, 88-95.
[25] Peng, G.; Wargovich, M.J.; Dixon, D.A. Cancer. Lett. 2006, 238, 260-270.
[26] Braganhol, E.; Zamin, L.L.; Canedo, A.D.; Horn, F.; Tamajusuku, A.S.K.; Wink, M.R.; Salbego, C.; Battastini, A. Anti Cancer. Drugs. 2006, 17, 663-671.
[27] Lu, J.; Papp, L.V.; Fang, J.; Rodriguez-Nieto, S.; Zhivotovsky, B.; Holmgren, A. Cancer. Res. 2006, 66, 4410-4418.
[28] Kumar, N.; Shibata, D.; Helm, J.; Coppola, D.; Malafa, M. Front. Biosci. 2007, 12, 2309-2315.
[29] Pu, F.; Mishima, K.; Irie, K.; Motohashi, K.; Tanakaet, Y.; Orito, K.; Egawa, T.; Kitamura, Y.; Egashira, N.; Iwasaki, K.; Fujiwara, M. J. Pharm. Sci. 2007, 104, 329-334.
[30] Mandel, S.; Weinreb, O.; Amit, T.; Youdim, M.B.H. J. Neurochem. 2004, 88, 1555-1569.
[31] Weinreb, O.; Mandel, S.; Amit, T.; Youdim, M.B.H. J. Nutr. Biochem. 2004, 15, 506-516.
[32] Coskun, O.; Kanter, M.; Korkmaz, A.; Oter, S. Pharm. Res. 2005, 51, 117-123.
[33] Leopoldini, M.; Russo, N.; Chiodo, S.; Toscano, M. J. Agric. Food Chem. 2006, 54, 96343-96351.
[34] Tipoe, G.L.; Leung, T.M.; Hung, M.W.; Fung, M.L. Cardiovasc. Hematol. Disord. Drug Targets. 2007, 7, 135-144.
[35] Weinreb, O.; Amit, T.; Youdim, M.B.H. Free Radic. Biol. Med. 2007, 43, 546-556.
[36] Strobel, P.; Allard, C.; Perez-Acle, T.; Calderon, R.; Aldunate, R.; Leighton, F. Biochem. J. 2005, 386, 471-478.
[37] Johnston, K.; Sharp, P.; Clifford, M.; Morgan, L. FEBS Lett. 2005, 579, 1653-1657.
[38] Fiorani, M.; Accorsi, A. Bt. J. Nutr. 2007, 94, 338-345.
[39] Brookes, P.S.; Digerness, S.B.; Parks, D.A.; Darley, V. Free Radic. Biol. Med. 2002, 32, 1220-1228.
[40] Fiorani, M.; Guidarelli, A.; Blasa, M.; Azzolini, C.; Candiracci, M.; Piatti, E.; Cantoni, O. The J. Nutr. Biochem. 2009, 10, 1016-1024.
[41] Dorta, D.J.; Pigoso, A.A.; Mingatto, F.E.; Rodrigues, T.; Prado, I.M.R.; Helena, A.F.C.; Uyemura, S.A.; Santos, A.C.; Carlos, C. Chem. Biol. Interact. 2005, 152, 67-78.
[42] Trumbeckaite, S.; Bernatoniene, J.; Majiene, D.; Jakštas, V.; Savickas, A.; Toleikis, A. Biomed. Pharmacother. 2006, 60, 245-248.
[43] Mouria, M.; Gukovskaya, A.S.; Jung, Y.; Buechler, P.; Hines, O.; Reber, H.A.; Pandol, S.J. Int. J. Cancer. 2002, 98, 761-769.
[44] Susin, S.A.; Larochette, N.; Geuskens, M.; Kroemer, G. Methods. Enzymol. 2000, 322, 205-208.
[45] Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. J. Biol. Chem. 1951, 193, 265-275.
[46] Kristal, B.S.; Park, B.K.; Yu, B.P. J. Biol. Chem. 1996, 271, 6033-6038.
[47] Emaus, R.K.; Grunwald, R.; Lemasters, J.J. Biochim. Biophys. Acta. 1986, 850, 436-448.
[48] Cathcart, R.; Schwiers, E.; Ames, B.N. Anal. Biochem. 1983, 134, 111-116.
[49] Mosmann, T. J. Immunol. Methods. 1983, 65, 55-63.
[50] O'Rourke, B. Annu. Rev. Physiol. 2007, 69, 19-49.
[51] Musser, D.A.; Oseroff, A.R. Photochem. Photobiol. 1994, 59, 621-626.
[52] Soares, S.S.; Gutiérrez-Merino, C.; Aureliano, M. Aquat. Toxicol. 2007, 83, 1-9.
[53] Zamzami, N.; Kroemer, G. Nat. Rev. Mol. Cell Biol. 2001, 2, 67-71.
[54] Jonas, E.A. Exp. Neurol. 2009, 218, 203-212.
[55] Maciel, E.N.; Vercesi, A.E.; Castilho, R.F. J. Neurochem. 2001, 79, 1237-1245.
[56] Argaud, L.; Gateau-Roesch, O.; Chalabreysse, L.; Gomez, L. Cardiovasc. Res. 2004, 61, 115-122.
[57] Kumarswamy, R.; Chandna, S. Mitochondrion. 2009, 9, 1-8.
[58] Kowaltowski, A.J.; Castilho, R.F.; Vercesi, A.E. FEBS Lett. 1996, 378, 150-152.
[59] Valko, M.; Morris, H.; Cronin, M.T.D. Curr. Med. Chem. 2005, 12, 1161-1208.
[60] Wyllie, A. Nature. 1997, 389, 237-237.
[61] Younes, M.; Kayser, E.; Strubelt, O. Toxicology. 1991, 70, 141-149.
[62] Shukla, R.; Padhye, S.; Modak, M.; Ghaskadbi, S.S.; Bhonde, R.R. Rev. Diabet. Stud. 2007, 4, 33-43.
[63] Chandra, A.K.; Ghosh, R.; Chatterjee, A.; Sarkar, M. Mol. Cell. Biochem. 2007, 306, 189-200.
[64] Zhang, L.; Zhang, Y.; Xia, Q.; Zhao, X.M.; Cai, H.X.; Li, D.W.; Yang, X.D.; Wang, K.; Xia, Z.L. Food. Chem. Toxicol. 2008, 46, 155-160.
[65] Capella, L.S.; Gefé, M.R.; Silva, E.F.; Affonso, O.; Lopes, A.G.; Rumjanek, V.M.; Capella, M.A.M. Arch. Biochem. Biophys. 2002, 406, 65-72.
[66] Lei, W.H.; Liu, H.X.; Zhong, L.J.; Yang, X.D.; Wang, K. Sci. China. Ser. B. 2007, 52, 2775-2781.
[67] Roess, D.A.; Smith, S.M.L.; Winter, P.; Zhou, J.; Dou, P.; Baruah, B.; Trujillo, A.M.; Levinger, N.E.; Yang, X.D.; Barisas, B.G.; Crans, D.C. Chem. Biodivers. 2008, 5, 1558-1570.

槲皮素和茶多酚抑制VO(acac)₂导致的线粒体损伤和细胞毒性

Quercetin and green tea polyphenols inhibit the mitochondrial damages and cytotoxicity induced by VO(acac)₂

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