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Evaluation of the protective effects of α-tocopherol and retinol against ochratoxin A cytotoxicity

Published online by Cambridge University Press:  09 March 2007

A. Baldi ,
M. N. Losio ,
F. Cheli ,
R. Rebucci ,
L. Sangalli ,
E. Fusi ,
B. Bertasi ,
E. Pavoni ,
S. Carli  and
I. Politis
A. Baldi*
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
M. N. Losio
Affiliation:
Istituto Zooprofilattico Sperimentale (IZS) della Lombardia e dell'Emilia Romagna, 25100, Brescia, Italy
F. Cheli
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
R. Rebucci
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
L. Sangalli
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
E. Fusi
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
B. Bertasi
Affiliation:
Istituto Zooprofilattico Sperimentale (IZS) della Lombardia e dell'Emilia Romagna, 25100, Brescia, Italy
E. Pavoni
Affiliation:
Istituto Zooprofilattico Sperimentale (IZS) della Lombardia e dell'Emilia Romagna, 25100, Brescia, Italy
S. Carli
Affiliation:
Department of Veterinary Sciences and Technology for Food Safety, Veterinary Medicine Faculty, 20133, Milan, Italy
I. Politis
Affiliation:
Department of Animal Production, Agricultural University of Athens, Athens, Greece11855
*
*Corresponding author: Dr Antonella Baldi, fax +39 02 50315746, email [email protected]
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Abstract

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Ochratoxin A (OTA), a mycotoxin frequently present in food and feedstuffs, produces a wide range of toxic effects, including cell death via lipid peroxidation. In one human and four animal cell lines we determined the half lethal concentration (LC50) of OTA, its effect on reactive oxygen species (ROS) production, and its ability to induce cytochrome p450 activity. We also examined the protective effect of α-tocopherol and all-trans-retinol in the most sensitive cell lines (i.e. bovine mammary epithelia, for which LC50 was 0·8μg/ml (24h), and Madin Darby canine kidney, for which LC50 was 4·3μg/ml (48h)). Pre-incubation for 3h with either antioxidant significantly (P<0·05) ameliorated the OTA-induced reduction in cell viability and significantly decreased (P<0·05) ROS production. These findings indicate that oxidative stress is an important factor in OTA cytotoxicity. Supplementation with antioxidant molecules may counteract the short-term toxicity of this mycotoxin.

Keywords

Ochratoxin AAntioxidantsCell culturesReactive oxygen species
Type
Short communication
Information
British Journal of Nutrition , Volume 91 , Issue 4 , April 2004 , pp. 507 - 512
Copyright
Copyright © The Nutrition Society 2004

References

Atroshi, F, Rizzo, A, Westermarck, T & Ali-Vehamas, T (2002) Antioxidant nutrients and mycotoxins. Toxicology 180, 151–167.CrossRefGoogle ScholarPubMed
Baldi, A, Fusi, E, Rebucci, R, Pinotti, L & Cheli, F (2002) In vitro cytotoxicity of aflatoxin B 1, M 1 and ochratoxin A and protective effects of antioxidants. J Dairy Sci 85, 29.Google Scholar
Baudrimont, I, Ahouandjivo, R & Creppy, EE (1997) Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture by several agents. Chem Biol Interact 104, 29–40.CrossRefGoogle ScholarPubMed
Bruinink, A, Rasonyi, T & Sidler, C, (1998) Differences in neurotoxic effects of ochratoxin A, ochracin and ochratoxin alpha in vitro. Nat Toxins 6, 173–177.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Bruinink, A & Sidler, C (1997) The neurotoxic effects of ochratoxin A are reduced by protein binding but are not affected by l -phenylalanine. Toxicol Appl Pharmacol 146, 173–179.CrossRefGoogle Scholar
Cheli, F, Politis, I, Rossi, L, Fusi, E & Baldi, A (2003) Effects of retinoids on proliferation and plasminogen activator expression in a bovine mammary epithelial cell line. J Dairy Res 70, 367–372.CrossRefGoogle Scholar
de Groene, EM, Jahn, A, Horbach, GJ & Fink-Gremmels, J (1996) Mutagenicity and genotoxicity of mycotoxin ochratoxin A. Environ Toxicol Pharmacol 1, 21–26.CrossRefGoogle ScholarPubMed
Donato, MT, Gómez-Lechón, MJ & Castell, JV (1993) A microassay for measuring cytochrome P450IA1 and P450IIB1 activities in intact human and rat hepatocytes cultured on 96 well plates. Anal Biochem 213, 29–33.CrossRefGoogle ScholarPubMed
Ferrufino-Guardia, EV, Tangni, EK, Larondelle, Y & Ponchaut, S (2000) Transfer of ochratoxin A during lactation: exposure of suckling via the milk of rabbits does fed a naturally contaminated feed. Food Addit Contam 17 167–175.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
Gekle, M, Schwerdt, G, Freudinger, R, Mildenberger, S, Wilflingseder, D, Pollack, V, Dander, M & Schramek, H (2000) Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations. J Pharmacol Exp Ther 293, 837–844.Google ScholarPubMed
Grosse, Y, Chekir-Ghedira, L, Huc, A, Obrecht-Pflumio, S, Dirheimer, G, Bacha, H & Pfohl-Leszkowicz, A (1997) Retinol, ascorbic acid and alpha-tocopherol prevent DNA adduct formation in mice with the mycotoxins ochratoxin A and zearalenone. Cancer Lett 114, 225–229.CrossRefGoogle ScholarPubMed
Hallén, IP, Breitholtz-Emanuelsson, A, Hult, K, Olsen, M & Oskarsson, A (1998) Placental and lactational transfer of ochratoxin A in rats. Nat Toxins 6, 43–49.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Hult, K, Teiling, A & Gatenback, S (1976) Degradation of ochratoxin A by the ruminant. Appl Environ Microbiol 32, 443–444.CrossRefGoogle ScholarPubMed
Hussein, HS & Brasel, JM (2001) Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology 167, 101–134.CrossRefGoogle ScholarPubMed
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 Risks to Humans, (56), pp.26– 32. Geneva: International Agency for Research on Cancer.Google Scholar
Joint FAO/WHO Expert Committee on Food Additives (2001) Monographs and Evaluations. JECFA-Monographs. http://www.inchem.org/documents/jecfa/jecmono/v47je04.htm.Google Scholar
Kanthasamy, AG, Ardelt, B, Malave, A, Mills, EM, Powley, TL, Borowitz, JL & Isom, GE (1997) Reactive oxygen species generated by cyanide mediate toxicity in rat pheochromocytoma cells. Toxicol Lett 93, 47–54.CrossRefGoogle ScholarPubMed
McDowell, LR & Cunha, CJ (1989) Vitamin A.In Vitamins in Animal Nutrition. Comparative Aspects to Human Nutrition, pp.10–54 [Cunha, TJ, editor]. San Diego, CA: Academic Press Inc.CrossRefGoogle Scholar
Omar, RF, Rahimtula, AD & Bartsch, H (1991) Role of cytochrome P450 in ochratoxin A-stimulated lipid peroxidation. J Biochem Toxicol 6, 203–209.CrossRefGoogle ScholarPubMed
Petzinger, E & Ziegler, K (2000) Ochratoxin A from a toxicological perspective. J Vet Pharmacol Ther 23, 91–98.CrossRefGoogle ScholarPubMed
Ribelin, WE, Fukushima, K & Still, PE (1978) The toxicity of ochratoxins to ruminants. Can J Comp Med 42, 172–177.Google ScholarPubMed
Robbana-Barnat, S, Lafarge-Frayssinet, C & Frayssinet, C (1989) Use of cell cultures for predicting the biological effects of mycotoxins. Cell Biol Toxicol 5, 217–226.CrossRefGoogle ScholarPubMed
SAS Institute, Inc. (1985) SAS ® User's Guide: Statistics, Cary, NC: SAS Institute, Inc, version 5.Google Scholar
Schaaf, GJ, Nijmaijer, SM, Maas, RFM, Roestenberg, P, de Groene, EM & Fink-Gremmels, J (2002) The role of oxidative stress in the ochratoxin A-mediated toxicity in the proximal tubular cells. Biochim Biophys Acta 1588, 149–158.CrossRefGoogle ScholarPubMed
Schwerdt, G, Freudinger, R, Silbernagl, S & Gekle, M (1999) Ochratoxin A-binding proteins in rat organs and plasma and in different cell lines of the kidney. Toxicology 135, 1–10.CrossRefGoogle ScholarPubMed
Tesoriere, L, Bongiorno, A, Pintaudi, AM, D'Anna, R, D'Arpa, D & Livrea, MA (1996) Synergistic interactions between vitamin A and vitamin E against lipid peroxidation in phospatidylcholine liposomes. Arch Biochem Biophys 326, 57–63.CrossRefGoogle Scholar
Yamazaki, H & Shimada, T (1999) Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by human cytochrome P450 enzymes. Xenobiotica 29, 231–241.CrossRefGoogle ScholarPubMed
Zhang, P & Omaye, ST (2001) β-Carotene: interactions with α-tocopherol and ascorbic acid in microsomal lipid peroxidation. J Nutr Biochem 12, 38–45.CrossRefGoogle ScholarPubMed