Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-15T05:21:37.142Z Has data issue: false hasContentIssue false
  • English
  • Français

Cyanidin-3-O-β-glucopyranoside, a natural free-radical scavenger against aflatoxin B1- and ochratoxin A-induced cell damage in a human hepatoma cell line (Hep G2) and a human colonic adenocarcinoma cell line (CaCo-2)

Published online by Cambridge University Press:  08 March 2007

M. C. Guerra ,
F. Galvano ,
L. Bonsi ,
E. Speroni ,
S. Costa ,
C. Renzulli  and
R. Cervellati
M. C. Guerra*
Affiliation:
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40 126 Bologna, Italy
F. Galvano
Affiliation:
Department of Agro-forestry, Environmental Science and Technology, University of Reggio Calabria, Piazza San Francesco 7, Reggio Calabria, Italy
L. Bonsi
Affiliation:
Institute of Histology and General Embryology, University of Bologna, Via Belmeloro 8, Bologna, Italy
E. Speroni
Affiliation:
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40 126 Bologna, Italy
S. Costa
Affiliation:
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40 126 Bologna, Italy
C. Renzulli
Affiliation:
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40 126 Bologna, Italy
R. Cervellati
Affiliation:
Department of Chemistry ‘G. Ciamician', University of Bologna, Via Selmi 2, Bologna, Italy
*
*Corresponding author: Professor Maria Clelia Guerra, fax +39 51 248862, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Recent findings have suggested that oxidative damage might contribute to the cytotoxicity and carcinogenicity of aflatoxin B1 (AFB1). Induction of oxidative stress also plays an important role in the toxicity of another mycotoxin, ochratoxin A (OTA). In the present study, the protective effect of cyanidin-3-O-β-glucopyranoside (C-3-G; an anthocyanin contained in oranges, blackberries, strawberries and cranberries) against AFB1- and OTA-induced cytotoxicity was investigated in a human hepatoma-derived cell line (Hep G2) and a human colonic adenocarcinoma cell line (CaCo-2). The ability of C-3-G to reduce the production of reactive oxygen species (ROS), the inhibition of protein and DNA synthesis and the apoptosis caused by the two mycotoxins was also investigated in both cell lines. Our experiments proved the significant cytoprotective effect of C-3-G in vitro against OTA- and AFB1-induced cell damage. In particular, 24 h of pretreatment with 50 μm-C-3-G inhibited the cytotoxicity of 10 μm-AFB1 (by 35 %) and of 10 μm-OTA (by 25 %) in Hep G2 cells (P<0·001) and of 10 μm-AFB1 (by 10 %, P<0·01) and of 10 μm-OTA (by 14 %, P<0·05) in CaCo-2 cells. Moreover, 50 μm-C-3-G attenuated ROS production induced by the two toxins in both cell lines (P<0·05). Inhibition of DNA and protein synthesis induced by the mycotoxins was counteracted by pretreatment with the antioxidant at 50 μm. Similarly, apoptotic cell death was prevented as demonstrated by a reduction of DNA fragmentation and inhibition of caspase-3 activation. The in vitro free-radical scavenging capacity of the anthocyanin was tested with the Briggs–Rauscher oscillating reaction. This system works at pH approximately 2. The results showed good scavenging power, in accordance with the observed inhibition of ROS production.

Keywords

MycotoxinsCyanidin-3-O-β-glucopyranosideHep G2 cellsCaCo-2 cells
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 2 , August 2005 , pp. 211 - 220
Copyright
Copyright © The Nutrition Society 2005

References

Abel, S & Gelderblom, WC (1998) Oxidative damage and fumonisin B1-induced toxicity in primary rat hepatocytes and rat liver in vivo. Toxicology 131, 121–131.CrossRefGoogle ScholarPubMed
Aboobaker, VS, Sarma, N, Goswami, NU & Bhattacharya, RK (1997) Inhibition of microsomal activation of aflatoxin B 1, by 3-dehydroretinol and 3-dehydroretinyl palmitate. Indian J Exp Biol 35, 1125–1127.Google Scholar
Amstad, P, Levy, A, Emeir, H & Cerulti, P (1984) Evidence for membrane-medicated chromosomal damage by afflatoxin B1 in human lymphocytes. Carcinogenesis 5, 719–723.CrossRefGoogle Scholar
Atroshi, F, Parantainen, J, Kangasniemi, R & Sankari, S (1987) Sialic acid, glutathione metabolism, and electrical conductivity in bovine mastitis udder tissue. J Anim Physiol Anim Nutr 58, 200–207.CrossRefGoogle Scholar
Baudrimont, I, Betbeder, AM, Gharbi, A, Pfohl-Leszkowicz, A, Dirheimer, G & Creppy, EE (1994) Effect of superoxide dismutase and catalase on the nephrotoxicity induced by subchronical administration of ochratoxin A in rats. Toxicology 89, 101–111.CrossRefGoogle ScholarPubMed
Belmadani, A, Steyn, PS, Tramu, G, Betbeder, AM, Baudrimont, I & Creppy, EE (1999) Selective toxicity of ochratoxin A in primary cultures from different brain regions. Arch Toxicol 73, 108–114.CrossRefGoogle ScholarPubMed
Bennett, JW & Keller, NP (1997) Mycotoxins and their prevention Fungal Biotechnology, pp. 265–273 [Anke, T, editor]. Weinheim: International Thompson Publishing Company.Google Scholar
Bradford, MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle Scholar
Briggs, T & Rauscher, W (1973) An oscillating iodine clock. J Chem Educ 50, 496.CrossRefGoogle Scholar
Cavin, C, Holzhäser, D, Constable, A, Huggett, AC & Schilter, B (1998) The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B 1 -induced genotoxicity through a dual mechanism. Carcinogenesis 19, 1369–1375.CrossRefGoogle ScholarPubMed
Cervellati, R, Höner, K, Furrow, SD, Neddens, C & Costa, S (2001) The Briggs–Rauscher reaction as a test to measure the activity of antioxidants. Helv Chim Acta 84, 3533–3547.3.0.CO;2-Y>CrossRefGoogle Scholar
Cervellati, R, Höner, K, Furrow, SD, Mazzanti, F & Costa, S (2004a) An experimental mechanistic investigation of the complexities arising during inhibition of the Briggs–Rauscher reaction by antioxidants. Helv Chim Acta 87, 133–155.CrossRefGoogle Scholar
Cervellati, R, Innocenti, G, Dall'Acqua, S, Costa, S & Sartini, E (2004) Polyphenols from Polygala spp. and their antioxidant activity. Chem Biodivers 1, 415–425.CrossRefGoogle ScholarPubMed
Cervellati, R, Speroni, E, Govoni, P, Guerra, MC, Costa, S, Arnold, UW & Stuppner, H (2004c) Wulfenia carinthiaca Jacq., antioxidant and pharmacological activities. Z Naturforschung 59, 255–262.CrossRefGoogle ScholarPubMed
Cochereau, C, Sanchez, D & Creppy, EE (1997) Tyrosine prevents capsaicin-induced protein synthesis inhibition in cultured cells. Toxicology 117, 133–139.CrossRefGoogle ScholarPubMed
Fimognari, C, Berti, F, Nüsse, M, Cantelli-Forti, G & Hrelia, P (2004) Induction of apoptosis in two human leukemia cell lines as well as differentiation in human promyelocytic cells by cyanidin-3- O -β-glucopyranoside. Biochem Pharmacol 67, 2047–2056.CrossRefGoogle ScholarPubMed
Galvano, F, La Fauci, L, Lazzarino, G, Fogliano, V, Ritieni, A, Ciappellano, S, Battistini, NC, Tavazzi, B & Galvano, G (2004) Cyanidins: metabolism and biological properties. J Nutr Biochem 15, 2–11.CrossRefGoogle ScholarPubMed
Galvano, F, Piva, A, Ritieni, A & Galvano, G (2001) Dietary strategies to counteract the effects of mycotoxins: a review. J Food Prot 64, 120–131.CrossRefGoogle ScholarPubMed
Gautier, JC, Holzhaeuser, D, Markovic, J, Gremaud, E, Schilter, B & Turesky, RJ (2001) Oxidative damage and stress response from ochratoxin A exposure in rats. Free Radic Biol Med 30, 1089–1098.CrossRefGoogle ScholarPubMed
Gramenitsky, EM (1963) Supravital Staining of Cells and Tissues. pp. 151. Leningrad: Medgiz.Google Scholar
Höner, K & Cervellati, R (2002) Measurements of the antioxidant capacity of fruits and vegetables using the BR reaction method. Eur Food Res Technol 215, 437–442.Google Scholar
Höner, K, Cervellati, R & Neddens, C (2002) Measurements of the in vitro antioxidant activity of German white wines using a novel method. Eur Food Res Technol 214, 356–360.Google Scholar
International Agency for Research on Cancer (1993) Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. IARC Monographs on the Evaluation of Carcinogenic Risk to Humans, vol. 56. Lyon: IARC.Google Scholar
Knasmüller, S, Parzefall, W & Sanyal, R (1998) Use of metabolic competent human hepatoma cells for the detection of mutagens and antimutagens. Mutat Res 402, 185–202.CrossRefGoogle ScholarPubMed
Kuiper-Goodman, T & Scott, PM (1989) Risk assessment of the mycotoxin ochratoxin A. Biomed Environ Sci 2, 179–248.Google ScholarPubMed
Massey, TE, Stewart, RK, Daniels, JM & Liu, L (1995) Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B 1 carcinogenicity. Proc Soc Exp Biol Med 208, 213–227.CrossRefGoogle ScholarPubMed
Monnet-Tschudi, F, Sorg, O, Honegger, P, Zurich, MG, Huggett, AC & Schilter, B (1997) Effects of the naturally occurring food mycotoxin ochratoxin A on brain cells in culture. Neurotoxicology 18, 831–839.Google ScholarPubMed
Omar, RF & Rahimtula, AD (1983) Possible role of an iron–oxygen complex in 4(S)-4-hydroxyochratoxin A formation by rat liver microsomes. Biochem Pharmacol 46, 2073–2081.CrossRefGoogle Scholar
Omar, RF, Hasinoff, BB, Mejilla, F & Rahimtula, AD (1990) Mechanism of ochratoxin A stimulated lipid peroxidation. Biochem Pharmacol 40, 1183–1191.Google Scholar
Passamonti, S, Vrhovsek, U, Vanzo, A & Mattivi, F (2003) The stomach as a site for anthocyanins absorption from food. FEBS Lett 544, 210–213.CrossRefGoogle ScholarPubMed
Pietta, PG (2000) Flavonoids as antioxidants. J Nat Prod 63, 1035–1042.CrossRefGoogle ScholarPubMed
Rahimtula, AD, Bereziat, JC, Bussacchini-Griot, V & Bartsch, H (1988) Lipid peroxidation as a possible cause of ochratoxin A toxicity. Biochem Pharmacol 37, 4469–4477.Google Scholar
Renzulli, C, Galvano, F, Pierdomenico, L, Speroni, E & Guerra, MC (2004) Effects of rosmarinic acid against aflatoxin B1 and ochratoxin A-induced cell damage in a human hepatoma cell line (Hep G2). J Appl Toxicol 24, 289–296.CrossRefGoogle Scholar
Rice-Evans, CA, Miller, NJ & Paganga, G (1996) Structure–antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933–956.CrossRefGoogle ScholarPubMed
Rizzo, AF, Atroshi, F, Ahotupa, M, Sankari, S & Elovaara, E (1994) Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin. J Vet Med Assoc 41, 81–90.Google Scholar
Speroni, E, Cervellati, R, Govoni, P, Guizzardi, S, Renzulli, C & Guerra, MC (2003) Efficacy of different Cynara scolymus preparations on liver complaints. J Ethnopharmacol 86, 203–211.CrossRefGoogle ScholarPubMed
Steyn, PS & Stander, MA (1999) Mycotoxins as causal factors of diseases in humans. J Toxicol Toxin Rev 18, 229–243.Google Scholar
Talavéra, S, Felgines, C, Texier, O, Besson, C, Lamaison, JL & Rémésy, C (2003) Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. J Nutr 133, 4178–4182.CrossRefGoogle ScholarPubMed
Talavéra, S, Felgines, C, Texier, O, Besson, C, Manach, C, Lamaison, JL & Remesy, C (2004) Anthocyanins are efficiently absorbed from the small intestine in rats. J Nutr 134, 2275–2279.Google Scholar
Vinson, JA, Dabbagh, YA, Serry, MM & Jang, J (1995) Plant flavonoids, especially tea flavonols, are powerful antioxidant using an in vitro oxidation model for heart disease. J Agric Food Chem 43, 5677–5684.Google Scholar
Wang, SY & Stretch, AW (2001) Antioxidant capacity in cranberry is influenced by cultivar and storage temperature. J Agric Food Chem 49, 969–974.Google Scholar
Yin, JJ, Smith, MJ, Eppley, RM, Page, SW & Sphon, JA (1998) Effects of fumonisin B 1 on lipid peroxidation in membranes. Biochim Biophys Acta 1371, 134–142.CrossRefGoogle ScholarPubMed