Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

Nutrition & Metabolism

Hassen Bacha²  Lazhar Zourgui⁴  Hédi Ben Mansour¹  Yousra Ayed²  Chayma Bouaziz²  Dalel Brahmi³ 

[1] Laboratoire de Biochimie, Faculté de Pharmacie, Monastir, Rue Avicenne 5000 Monastir, Tunisia;Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia;Research unit of Macromolecular Biochemistry & Genetic, Faculty of Sciences Gafsa - 2112 Gafsa, Tunisia;Higher Institute of Applied Biology ISBAM Medenine university of Gabes, Tunisia

关键词: Hepatopretective;    Genotoxicity;    Oxidative Stress;    Aflatoxin B1;    Cactus;   

Others  :  820278
DOI  :  10.1186/1743-7075-8-73

 received in 2011-06-20, accepted in 2011-10-18,  发布年份 2011

【 摘 要 】

Background

Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.

Methods

Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.

Results

Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.

Conclusion

We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.

【 授权许可】

   
2011 Brahmi et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics 2002. CA Cancer J Clin 2005, 55:74-108.
• [2]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics. CA Cancer J Clin 2009, 59:225-49.
• [3]Okuda K: Hepatocellular carcinoma. J Hepatol 2000, 32:225-37.
• [4]Bartsch H, Montesano R: Relevance of nitrosamines to human cancer. J Carcinog 1984, 5:1381-93.
• [5]Ribes J, Cleries R, Esteban L, Moreno V, Bosch FX: The influence of alcohol consumption and hepatitis B and C infections on the risk of liver cancer in Europe. J Hepatol 2008, 49:233-42.
• [6]Bennett JW, Klich M: Mycotoxins. Clin Microbiol Rev 2003, 16:497-516.
• [7]Fink-Gremmels J: Mycotoxins: their implications for human and animal health. Vet Q& AArhive 1999, 21:115-120.
• [8]Cullen JM, Newberne PM: Acute hepatotoxicity of aflatoxins. In The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance. Edited by Eaton DL, Groopman JD. Academic Press, London; 1993.
• [9]International Agency for Research on Cancer (IARC): Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 2002, 82:1-556.
• [10]Roberts TA, Baird-Parker AC, Tompkin RB: Toxigenic fungi: Aspergillus. Microorganisms in Food. 5 Microbiological Specification of Food Pathogens-ICMSF. Volume Chapter 19. Blackie Academic and Professional, London; 1996::347-38.
• [11]Sharma RA, Farmer PB: Biological relevance of adduct detection to the chemoprevention of cancer. Clin Cancer Res 2004, 10:4901-4912.
• [12]Klein PJ, Van Vleet TR, Hall JO, Coulombe RA Jr: Biochemical factors underlying the age-related sensitivity of turkeys to aflatoxin B (1). Comp Biochem Physiol part C 2002, 132:193-201.
• [13]Shu Yuan Zhong-Wel, Xu Fei, Yang Hui, Chen Yang-ER, Yuan Ming, Xu Mo-Yun, Xue Li-Wei, Xu Xiao-Chao, Hong-Huilin : Mg-protoporphyrin, haem and sugar signals double cellular total RNA against herbicide and high-light-derived oxidative stress. Plant Cell Environ Plant 2011, in press.
• [14]Souza MF, Tome AR, Rao VS: Inhibition by the bioflavonoid ternatin of aflatoxin B1-induced lipid peroxidation in rat liver. J Pharm Pharmacol 1999, 51:125-129.
• [15]Okuno M, Kojima S, Moriwaki H: Chemoprevention of hepatocellular carcinoma: concept, progress and perspectives. J Gastroenterol Hepatol 2001, 6:1329-35.
• [16]Kensler TW, Quian GS, Chen JG, Groopman JD: Translational strategies for cancer prevention in liver. J Natl Cancer Inst 2003, 3:321-9.
• [17]Heber D: Vegetables, fruits and phytoestrogens in the prevention of diseases. J Postgrad Med 2004, 50:145-149.
• [18]Acevedo A, Fonseca E, Viguer JM, Contreras F: Use of the peroxidise antiperoxidase technic in cytologic smears in pemphigus vulgaris. Med Cutan Ibero Lat Am 1985, 13:237-241.
• [19]Stintzing FC, Stintzing AS, Carle R, Frei B, Wrolstad RE: Color and antioxidant properties of cyanidin-based anthocyanin pigments. J Agric Food Chem 2002, 50:6172-6181.
• [20]Ramadan MF, Morsel JT: Oil cactus pear (Opuntia ficus-indica). Food Chem 2003, 82:339-345.
• [21]Stintzing FC, Carle R: Cactus stems (Opuntia spp.): a review on their chemistry, technology, and uses. Mol Nutr Food Res 2005, 49:175-194.
• [22]Tesoriere L, Fazzari M, Allegra M, Livrea MA: Biothiols, taurine, and lipid-soluble antioxidants in the edible pulp of Sicilian cactus pear (Opuntia ficus-indica) fruits and changes of bioactive juice components upon industrial processing. J Agric Food Chem 2005, 20:7851-7855.
• [23]Galati EM, Mondello MR, Giuffrida D, Dugo G, Miceli N, Pergolizzi S, Taviano MF: Chemical characterization and biological effects of Sicilian Opuntiaficusindica (L.) Mill. fruit juice: antioxidant and antiulcerogenic activity. Agric Food Chem 2003, 51:4903-4908.
• [24]Kuti JO: Antioxidant compounds from four Opuntia cactus pear fruit varieties. Food Chem 2004, 85:527-533.
• [25]Tesoriere L, Butera D, Pintaudi M, Allegra M, Livrea MA: Supplementation with cactus pear (Opuntiaficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with Vit. C Am J Clin Nutr 2004, 80:391-395.
• [26]Zou DM, Brewer M, Garcia F, Feugang JM, Wang J, Zang R, Liu H, Zou C: Cactus pear: anatural product in cancer chemoprevention. Nutrition Journal 2005, 4:25-36. BioMed Central Full Text
• [27]Galati EM, Mondello MR, Lauriano ER, Traviano MF, Galluzzo M, Miceli N: Opuntiaficus-indica (L.) Miller fruit juice protects liver from carbon tetrachloride induced injury. Phytother Res 2005, 19:796-800.
• [28]Zourgui L, Imen AB, Yosra A, Hassen B, Wafa H: The antigenotoxic activities of cactus (Opuntiaficus-indica) cladodes against the mycotoxinzearalenone in Balb/c mice: prevention of micronuclei, chromosome aberrations and DNA fragmentation. Food Chem Toxicol 2009, 47:662-667.
• [29]Bradford MM: A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal Biochem 1976, 72:248-54.
• [30]Aust SD, Morehouse LA, Thomas CE: Role of metals in oxygen radical reactions. Journal of Free Radicals in Biology and Medicine 1985, 1:3-25.
• [31]Mercier Y, Gatellier P, Renerre M: Lipid and protein oxidation in vitro, and antioxidant potential in meat from Charolais cows finished on pasture or mixed diet. Meat Sci 2004, 66:467-473.
• [32]Evans EP, Breckon G, Ford CE: An air drying method for meiotic preparation from mammalian tests. Cytogenet 1960, 3:613-616.
• [33]Savage JRK: Classification and relationships of induced chromosomal structural changes. J Med Genet 1975, 12:103-122.
• [34]Maron DM, Ames BN: Revised methods for the Salmonella mutagenicity test. Mutat Res 1983, 113:173-215.
• [35]Quillardet P, Hofnung M: The SOS Chromotest, a colorimetric bacterial assay for genotoxins: procedures. Mutat Res 1985, 147:65-78.
• [36]Roebuck BD, Liu YL, Rogers AE, Groopman JD, Kensler TW: Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry. Cancer Res 1991, 51:5501-5506.
• [37]Cullen JM, Newberne PM: Acute hepatotoxicity of aflatoxins. In Toxicol Aflatoxins. Edited by Eaton DL, Groopman JD. San Diego, California: Academic Press; 1994:3-26.
• [38]Roebuck BD, Maxuitenko Y: Biochemical mechanisms and biological implications of the toxicity of aflatoxins as related to aflatoxin carcinogenesis. In The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance. Edited by Eaton DL, Groopman JD. New York: Academic Press; 1994:27-43.
• [39]Kim HS, Kwack SJ, Lee BM: Lipid peroxidation, antioxidant enzymes, and benzo[a]pyrene-quinones in the blood of rats treated with benzo[a]pyrene. Chem Biol Interact 2000, 127:139-150.
• [40]Dotan Y, Lichtenberg D, Pinchuk I: Lipid peroxidation cannot be used as a universal criterion of oxidative stress. Prog Lipid Res 2004, 43:200-227.
• [41]Preetha SP, Kanniappan M, Selvakumar E, Nagaraj M, Varalakshmi P: Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats. Comp Biochem Physiol C Comp Pharmacol 2006, 143:333-339.
• [42]Amstad P, Levy A, Emerıt I, Ceruttı P: Evidence for membrane mediated chromosomal damage by aflatoxin b1 in human lymphocytes. Carcinogenesis 1984, 5:719-723.
• [43]Abdel-Wahhab MA, Aly SE: Antioxidants and radical scavenging properties of vegetable extracts in rats fed aflatoxin-contaminated diet. J Agric Food Chem 2003, 51:2409-2414.
• [44]Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A: Protein carbonylation in human diseases. Trends Mol Med 2003, 9:169-176.
• [45]Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R: Protein carbonyl groups as biomarkers of oxidative damage in human disease. Clin Chim Acta 2003, 329:23-38.
• [46]Okada S: Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals. Pathol Int 1996, 46:311-332.
• [47]Ritossa F: A new puffing pattern induced by temperature shock and DNP in Drosophila. Experienta 1962, 18:571-573.
• [48]Welch WJ: How cells respond to stress. Sci Am 1993, 5:560-564.
• [49]Voellmy R: Sensing stress and responding to stress. In Stress Inducible Cellular Responses. Edited by Feige U, Morimoto RI, Yahara I, Polla B. Birkhäuser-Verlag, Basel, Switzerland; 1996:121-137.
• [50]Zou J, Salminen WF, Roberts SM, Voellmy R: Correlation between glutathione oxidation and trimerization of heat shock factor 1, an early step in stress induction of the Hsp response. Cell Stress Chaprones 1998, 3:130-141.
• [51]Freeman ML, Borelli MJ, Meredith MJ, Lepock JR: On the path to the heat shock response: destabilisation and formation of partially folded protein intermediates, a consequence of protein thiol modification. Free Radic Biol Med 1999, 26:737-745.
• [52]Beyersmann D, Hechtenberg S: Cadmium, gene regulation, and cellular signaling in mammalian cells. Toxicol Appl Pharmacol 1997, 144:247-261.
• [53]Fehrenbach E, Northoff H: Free radicals exercise apoptosis and heat shock proteins. Immunol Rev 2001, 7:66-89.
• [54]Zourgui L, Golli EE, Bouaziz C, Bacha H, Hassen W: Cactus (Opuntia ficus indica) Cladodes prevent oxidative damage induced by the mycotoxin zearalenone in Balb/c mice. Food Chem Toxicol 2008, 46:1817-1824.
• [55]Park EH, Kahng JH, Paek EA: Studies on the pharmacological actions of cactus: identification of is anti-inflammatory effect. Arch Pharm Res 1998, 21:30-34.
• [56]Shim HC, Hwang HJ, Kang KJ, Lee BH: An antioxidative and anti inflammatory agent for potential treatment of osteoarthritis from Ecklonia cava. Arch Pharm Res 2006, 29:165-171.
• [57]Siriwardhana N, Jeon YJ: Antioxydative effect of cactus pear fruit (Opuntiaficusindica) extract on lipid peroxidation inhibition in oils and emulsion model systems. Eur Food Res Technol 2004, 219:369-376.
• [58]Preston RJ, Williams GM: DNA-reactive carcinogens: mode of action and human cancer hazard. Crit Rev Toxicol 2005, 35:673-683.
• [59]Abdel-Wahhab MA, Ahmed HH, Hagazi MM: Prevention of aflatoxin B1-initiated hepatotoxicity in rat by marine algae extracts. J Appl Toxicol 2006, 26:229-38.
• [60]Albertini RJ, Ardell SK, Judice SA, Jacobson S, Allegretta M: Hypoxanthine-guanine phosphoribosyltransferase reporter gene mutation for analysis of in vivo clonal amplification in patients with HTLV type 1-associated Myelopathy/Tropical spastic paraparesis. AIDS Res Hum Retroviruses 2000, 16:1747-1752.
• [61]Hagmar L, Brogger A, Hansteen IL, Heim S, Högstedt B, Knudsen L, Lambert B, Linnainmaa K, Mitelman F, Nordenson I: Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: nordic study group on the health risk of chromosome damage. Cancer Res 1994, 54:2919-2922.
• [62]Hagmar L, Bonassi S, Strömberg U, Mikoczy Z, Lando C, Hansteen IL, Montagud AH, Knudsen L, Norppa H, Reuterwall C, Tinnerberg H, Brogger A, Forni A, Högstedt B, Lambert B, Mitelman F, Nordenson I, Salomaa S, Skerfving S: Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health. Mutat Res 1998, 405:171-178.
• [63]Swierenga SH, Heddle JA, Sigal EA, Gilman JP, Brillinger RL, Douglas GR, Nestmann ER: Recommended protocols based on a survey of current practice in genotoxicity testing laboratories, IV. Chromosome aberration and sister-chromatid exchange in Chinese hamster ovary, V79 Chinese hamster lung and human lymphocyte cultures. Mutat Res 1991, 246:227-233.
• [64]Eaton DL, Gallagher EP: Mechanisms of aflatoxin carcinogenesis. Annu Rev PharmacolToxicol 1994, 34:135-172.
• [65]Abid-Essefi S, Baudrimont I, Hassen W, Ouanes Z, Mobio TA, Anane R, Creppy E, Bacha H: DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in cultured DOK, Vero and Caco-2 cells: prevention by vitamin E. Toxicol 2003, 192:237-248.
• [66]Ouanes Z, Ayed-Boussema I, Baati T, Creppy EE, Bacha H: Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17b estradiol, progesterone and Vitamine E. Mutat Res 2005, 565:139-149.
• [67]Abbès S, Ouanes Z, Ben Salah-Abbes J, Houas Z, Oueslati R, Bacha H, Othman O: The protective effect of hydrated sodium calcium aluminosilicate against haematological biochemical and pathological changes induced by zearalenone in mice. Toxicon 2006, 47:567-574.
• [68]Phillips TD: Dietary clay in the chemoprevention of aflatoxin induced disease. Toxicol Sci 1999, 52:118-126.
• [69]De Flora S: Problems and prospects in antimutagenesis and anticarcinogenesis. Mutat Res 1988, 202:279-83.
• [70]Shon MY, Choi SD, Kahng GG, Nam SH, Sung NJ: Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions. Food Chem Toxicol 2004, 42:659-666.
• [71]De Carvalho MCRD, Barca FNTV, Agnez-Lima LF, de Medeiros SRB: Evaluation of mutagenic activity in an extract of pepper tree stem bark (Schinus terebinthifolius Raddi). Enviro Mol Mutagen 2003, 42:185-191.
• [72]Ranchal I, Gonzalez R, Bello RI, Ferrin G, Hidalgo AB, Linares CI, Aguilar Melero P, Gonzalez Rubio S, Barrera P, Marchal T, Nakayama KI, de la malta M, Muntane J: The reduction of cell death and proliferation by P27 (Kip1) minimizes DNA damage in an experimental model of genotoxicity. Int J Cancer 2009, 125:2270-2280.
• [73]Chandra J, Samali A, Orrenius S: Triggering and modulation of apoptosis by oxidative stress. Free Radical Biol Med 2000, 29:323-333.
• [74]Feugang JM, Konarski P, Zou D, Stintzing FC, Zou C: Nutritional and medicinal use of cactus pear (Opuntia spp.) cladodes and fruits. Frontiers Biosci 2006, 11:2574-2586.