A Study of Single and Combined Cytotoxic Effects of Fumonisin B1, Aflatoxin B1 and Ochratoxin a on Human Mononuclear Blood Cells using Different Cytotoxic Methods

A Study of Single and Combined Cytotoxic Effects of Fumonisin B1, Aflatoxin B1 and Ochratoxin a on Human Mononuclear Blood Cells using Different Cytotoxic Methods

24059676

Contact

Mwanza Mulunda

Contact

Michael F Dutton

Contact

North-West University

A Study of Single and Combined Cytotoxic Effects of Fumonisin B1, Aflatoxin B1 and Ochratoxin a on Human Mononuclear Blood Cells using Different Cytotoxic Methods

Article Fingerprint

ReserarchID

PDDTMCHSOO

AI TAKEAWAY

Connecting with the Eternal Ground

Abstract

Several studies on cereals destined for animal or human consumption in South Africa and Africa have shown co-contaminations of mycotoxins. There is evidence to suggest that the simultaneous action of different mycotoxins at various concentrations might have synergistic, inhibitive or additive effects on human and animal cells. The aims of this study were to identify combined cytotoxic effects of three of the more commonly occurring mycotoxins (aflatoxin B1 (AFB1) fumonisin B1 (FB1) and ochratoxin A (OTA)) found in South African and other feeds using the methyl thiazoltetrazolium (MTT) cytotoxicity assay, the Comet assay and Flow Cytometry to detect apoptotic and necrotic cells after exposure to the three toxins. Human mononuclear blood cells (mononucleocytes) were exposed to the three mycotoxins both singularly and in combinations at two concentrations (5 and 40ng/ml for OTA and AFB1 and 5 and 40μg/ml for FB1) and at different exposure time of 12, 24 and 48Hours. Results obtained showed cell viability variations dependent on mycotoxin concentrations and time of exposure. In addition, synergistic effects were also observed at the higher doses of 40ng for OTA and AFB1) and 40μg/ml for FB1 of the three mycotoxins compared to combinations of lower doses.

References

68 Cites in Article

Reference Format

Edmond Creppy,Patrizia Chiarappa,Isabelle Baudrimont,Pietro Borracci,Serge Moukha,Maria Carratù (2004). Synergistic effects of fumonisin B1 and ochratoxin A: are in vitro cytotoxicity data predictive of in vivo acute toxicity?.
P Njobeh,M Dutton,A Makun (2010). Mycotoxins and human health: Significance, prevention and control.
S Hussein,M Brasel (2001). Toxicity, metabolism, and impact of mycotoxins on humans and animals.
Jonathan Williams,Jessica Grubb,Jerry Davis,Jia-Sheng Wang,Pauline Jolly,Nii-Ayi Ankrah,William Ellis,Evans Afriyie-Gyawu,Natalie Johnson,Abraham Robinson,Timothy Phillips (2010). HIV and hepatocellular and esophageal carcinomas related to consumption of mycotoxin-prone foods in sub-Saharan Africa.
Paul Turner,Sophie Moore,Andrew Hall,Andrew Prentice,Christopher Wild (2003). Modification of immune function through exposure to dietary aflatoxin in Gambian children..
Y Gong,A Hounsa,S Egal,P Turner,A Sutcliffe,A Hall,K Cardwell,C Wild (2004). Post-weaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa.
Jonathan Williams,Timothy Phillips,Pauline Jolly,Jonathan Stiles,Curtis Jolly,Deepak Aggarwal (2004). Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions.
J Wagacha,J Muthomi (2008). Mycotoxin problem in Africa: Current status, implications to food safety and health and possible management strategies.
R Riley (1998). Mechanistic interactions of mycotoxins: theoretical consideration.
H Yoo,W Norred,Riley Showker (1996). Elevated sphingoid bases and complex sphingolipid depletion as contributing factors in fumonisin-induced cytotoxicity.
A Merrill,E-M Schmelz,D Dillehay,S Spiegel,J Shayman,J Schroeder,R Riley,K Voss,E Wang (1997). Sphingolipids—The Enigmatic Lipid Class: Biochemistry, Physiology, and Pathophysiology.
G Shephard,L Van Der Westhuizen (1998). Liquid chromatographic determination of the sphinganine/sphingosine ratio in serum.
W Marasas,K Jaskiewics,F Venter,D Vanschalkwyk (1988). Fusarium moniliforme contamination of maize in oesophageal cancer areas in Transkei.
G Diaz,H Boermans (1994). Fumonisin toxicosis in domestic animals: a review.
Y Ueno,K Iijima,S-D Wang,Y Sugiura,M Sekijima,T Tanaka,C Chen,S-Z Yu (1997). Fumonisins as a possible contributory risk factor for primary liver cancer: A 3-year study of corn harvested in Haimen, China, by HPLC and ELISA.
J Fincham,W Marasas,J Taljaard,N Kriek,C Badenhorst,W Gelderblom,J Seier,C Smuts,M Faber,M Weight,W Slazus,C Woodroof,M Van Wyk,M Kruger,P Thiel (1992). Atherogenic effects in a non-human primate of Fusarium moniliformecultures added to a carbohydrate diet.
M Dutton (2009). The African Fusarium/maize disease.
Walter Marasas,Ronald Riley,Katherine Hendricks,Victoria Stevens,Thomas Sadler,Janee Gelineau-Van Waes,Stacey Missmer,Julio Cabrera,Olga Torres,Wentzel Gelderblom,Jeremy Allegood,Carolina Martínez,Joyce Maddox,J Miller,Lois Starr,M Sullards,Ana Roman,Kenneth Voss,Elaine Wang,Alfred Merrill (2004). Fumonisins Disrupt Sphingolipid Metabolism, Folate Transport, and Neural Tube Development in Embryo Culture and In Vivo: A Potential Risk Factor for Human Neural Tube Defects among Populations Consuming Fumonisin-Contaminated Maize.
Janee Gelineau‐van Waes,Lois Starr,Joyce Maddox,Francisco Aleman,Kenneth Voss,Justin Wilberding,Ronald Riley (2005). Maternal fumonisin exposure and risk for neural tube defects: Mechanisms in an in vivo mouse model.
Stacey Missmer,Lucina Suarez,Marilyn Felkner,Elaine Wang,Alfred Merrill,Kenneth Rothman,Katherine Hendricks (2006). Exposure to Fumonisins and the Occurrence of Neural Tube Defects along the Texas–Mexico Border.
G Devegowda,M Radu,A Nazar,H Swamy Mycotoxin picture worldwide: Novel solutions for their counteraction.
Stoycho Stoev (2008). Complex Etiology, Prophylaxis and Hygiene Control in Mycotoxic Nephropathies in Farm Animals and Humans.
Stoycho Stoev,Stefan Denev,Mike Dutton,Patrick Njobeh,Joseph Mosonik,Paul Steenkamp,Iordan Petkov (2010). Complex etiology and pathology of mycotoxic nephropathy in South African pigs.
S Stoev (2008). Mycotoxic nephropathies in farm animals' diagnostics, risk assessment and preventive measures.
J Fink-Gremmels,L Leistner (1990). Toxicological evaluation of moulds.
S Stoev,S Denev,M Dutton,B Nkosi (2009). Cytotoxic Effect of Some Mycotoxins and their Combinations on Human Peripheral Blood Mononuclear Cells as Measured by the MTT Assay.
Mulunda Mwanza,Lazlow Kametler,Alex Bonai,Veronika Rajli,Melinda Kovacs,Michael Dutton (2009). The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay.
F Meky,L Hardie,S Evans,C Wild (2001). Deoxynivalenol-induced immunomodulation of human lymphocyte proliferation and cytokine production.
N Singh,M Mccoy,R Tice,E Schneider (1988). A simple technique for quantitation of low levels of DNA damage in individual cells.
A Collins,A Oscoz,G Brunborg,I Gaivao,L Giovannelli,M Kruszewski,C Smith,R Stetina (1997). The comet assay: topical issues.
A Hartmann,E Agurell,C Beevers,S Brendler-Schwaab,B Burlinson,P Clay (2003). Recommendations for conducting the in vivo alkaline Comet assay.
Peter Delves,Seamus Martin,Dennis Burton,Ivan Roitt,Pedro Aparicio Alonso (2006). Roitt. Inmunología. Fundamentos (11a edición).
K Charoenpornsook,J Fitzpatrick,J Smith (1998). The effects of four mycotoxins on the mitogen stimulated proliferation of bovine peripheral blood mononuclear cells in vitro.
Mary Dombrink-Kurtzman,Tariq Javed,Glenn Bennett,John Richard,L Cote,William Buck (1993). Lymphocyte cytotoxicity and erythrocytic abnormalities induced in broiler chicks by fumonisins B1 and B2 and moniliformin fromFusarium proliferatum.
G Grabsch,G Wichmann,H Loffhagen,O Herbarth,A Muller (2006). Cytotoxicity assessment of gliotoxin and penicillic acid in Tetrahymenapyriformis.
C Lewis,J Smith,J Anderson,R Freshney (1999). Increased cytotoxicity of food-borne mycotoxins toward human cell lines in vitro via enhanced cytochrome p450 expression using the MTT bioassay.
J Timbrell (2001). Toxic Responses to Foreign Compounds.
Frederick Kiechle,Xinbo Zhang,Carol Holland-Staley (2004). The -omics Era and Its Impact.
D Vinatier,P Dufour,D Subtil (1996). Apoptosis: a programmed cell death involved in ovarian and uterine physiology.
Ana-Marija Domijan,Davor Želježić,Nevenka Kopjar,Maja Peraica (2006). Standard and Fpg-modified comet assay in kidney cells of ochratoxin A- and fumonisin B1-treated rats.
Peter Lutz,Liscia Manuel (1999). Maintenance of adenosine A<sub>1</sub>receptor function during long-term anoxia in the turtle brain.
Mário Mantovani,Marilanda Bellini,José Angeli,Rodrigo Oliveira,Ariane Silva,Lúcia Ribeiro (2008). β-Glucans in promoting health: Prevention against mutation and cancer.
F Minervini,F Fornelli,K Flynn (2004). Toxicity and apoptosis induced by the mycotoxins nivalenol, deoxynivalenol and fumonisin B1 in a human erythroleukemia cell line.
M Theumer (2003). Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats.
W Butler,G Neal (1977). Mode of action and human health aspects of aflatoxin carcinogenesis.
E Lillehoj (1991). Aflatoxin: an ecologically elicited activation signal.
Lyndon Foster,Katherine Kozak,Mark Loftus,Jacqueline Stevens,Ian Ross (1993). The polymerase chain reaction and its application to filamentous fungi.
K Raney,D Meyer,B Ketterer,T Harris,F Guengerish (1992). Glutathione conjugation of aflatoxin B-1 exo-and endo-epoxides by rats and human glutathione-S-transferases.
Yau-Huei Wei,Ching-Yow Lu,Teng-Nan Lin,Ru-Dong Wei (1985). Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation.
C Wild,P Turner (2002). The toxicology of aflatoxins as a basis for public health decisions.
C Wild,Y Gong (2010). Mycotoxins and human disease: a largely ignored global health issue.
Chayma Bouaziz,Ossama Sharaf El Dein,Emna El Golli,Salwa Abid-Essefi,Catherine Brenner,Christophe Lemaire,Hassen Bacha (2008). Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells.
Emna Golli‐bennour,Bochra Kouidhi,Amel Bouslimi,Salwa Abid‐essefi,Wafa Hassen,Hassen Bacha (2010). Cytotoxicity and genotoxicity induced by aflatoxin B1, ochratoxin A, and their combination in cultured Vero cells.
D Ringot,A Chango,Y-J Schneider,Y Larondelle (2006). Toxicokinetics and toxicodynamics of ochratoxin A, an update.
Kenneth Voss,Paul Howard,Ronald Riley,Raghubir Sharma,Thomas Bucci,Ronald Lorentzen (2002). Carcinogenicity and mechanism of action of fumonisin B1: a mycotoxin produced by Fusarium moniliforme (=F. verticillioides).
W Seefelder (2003). Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites.
(2003). 1975 annual summary report. [Abstracts of papers published during previous calendar year].
E Wang,W Norred,C Bacon,R Riley,A Merrill (1998). Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme.
G Bondy,J Pestka (2000). Immunomodulation by fungal toxins.
Martynova (1995). Fumonisin B1 modulates sphingomyelin cycle product levels and the expression of CD3 receptors in immunocompetent organs.
Claudia De Lorenzo,Rosanna Cozzolino,Andrea Carpentieri,Piero Pucci,Paolo Laccetti,Giuseppe D'alessio (2005). Biological properties of a human compact anti-ErbB2 antibody.
G Jenkins,William Tolleson,D Newkirk,Dean Roberts,Kenneth Rowland,Takeyori Saheki,Keiko Kobayashi,Paul Howard,William Melchoir (2000). Identification of fumonisin B1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies.
J Schroeder,H Crane,J Xia,D Liotta,A Merrill (1994). Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B1. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme..
C Huang,M Dieckeman,G Henderson,C Jones (1995). Repression of protein kinase C and stimulation of cyclic AMP response elements by Fumonisins, a fungal encoded toxin which is carcinogen.
Danica Ramljak,Richard Calvert,Paddy Wiesenfeld,Bhalchandra Diwan,Branimir Catipovic,Walter Marasas,Tommie Victor,Lucy Anderson,Wentzel Gelderblom (2000). A potential mechanism for fumonisin B1-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3β activity.
P Surai,J Dvorska (2005). Effects of mycotoxins on antioxidant status and immunity; InThe Mycotoxin Blue Book.
A Pier (1992). Major biological consequences of aflatoxicosis in animal production.
D Marin,I Taranu,R Bunaciu,F Pascale,D Tudor,N Avram,M Sarca,I Cureu,R Criste,V Suta,I Oswald (2002). Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin1.

Download References

Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

How to Cite This Article

24059676. 2014. \u201cA Study of Single and Combined Cytotoxic Effects of Fumonisin B1, Aflatoxin B1 and Ochratoxin a on Human Mononuclear Blood Cells using Different Cytotoxic Methods\u201d. Global Journal of Medical Research - B: Pharma, Drug Discovery, Toxicology & Medicine GJMR-B Volume 14 (GJMR Volume 14 Issue B2): .

More Citation Formats

Select Citation Style:

Download Citation

Download Article

GJMR Volume 14 Issue B2
Pg. 1- 19

Explore Journals Explore Volume Read This Issue

Journal Specifications

Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

Keywords

additive aflatoxin b1 carcinogenic cytotoxicity fumonisin b1 mononucleocytes mycototoxins ochratoxin a synergism

Submission ReceivedDecember 16, 2013
Peer Review Double Blind
Handling Editor
Accepted January 4, 2014
Published January 15, 2014

Version of record

v1.2

Issue date

June 3, 2014

Language

Experiance in AR

Explore published articles in an immersive Augmented Reality environment. Our platform converts research papers into interactive 3D books, allowing readers to view and interact with content using AR and VR compatible devices.

View in VR

Read in 3D

Your published article is automatically converted into a realistic 3D book. Flip through pages and read research papers in a more engaging and interactive format.

View in 3D

Article Matrices

Total Score: 102

Country: South Africa

Subject: Global Journal of Medical Research - B: Pharma, Drug Discovery, Toxicology & Medicine

Authors: Mwanza Mulunda, Michael F Dutton (PhD/Dr. count: 0)

View Count (all-time): 138

Total Views (Real + Logic): 4408

Total Downloads (simulated): 2190

Publish Date: 2014 06, Tue

Monthly Totals (Real + Logic):

Month 1: 35 views
Month 2: 29 views
Month 3: 64 views
Month 4: 30 views
Month 5: 46 views
Month 6: 43 views
Month 7: 41 views
Month 8: 33 views
Month 9: 26 views
Month 10: 34 views
Month 11: 27 views
Month 12: 16 views
Month 13: 49 views
Month 14: 22 views
Month 15: 33 views
Month 16: 40 views
Month 17: 26 views
Month 18: 20 views
Month 19: 18 views
Month 20: 22 views
Month 21: 39 views
Month 22: 19 views
Month 23: 26 views
Month 24: 31 views
Month 25: 26 views
Month 26: 33 views
Month 27: 29 views
Month 28: 35 views
Month 29: 28 views
Month 30: 36 views
Month 31: 27 views
Month 32: 33 views
Month 33: 29 views
Month 34: 21 views
Month 35: 31 views
Month 36: 35 views
Month 37: 26 views
Month 38: 34 views
Month 39: 14 views
Month 40: 24 views
Month 41: 28 views
Month 42: 17 views
Month 43: 31 views
Month 44: 18 views
Month 45: 25 views
Month 46: 29 views
Month 47: 16 views
Month 48: 46 views
Month 49: 29 views
Month 50: 30 views
Month 51: 38 views
Month 52: 29 views
Month 53: 18 views
Month 54: 20 views
Month 55: 36 views
Month 56: 42 views
Month 57: 19 views
Month 58: 25 views
Month 59: 24 views
Month 60: 14 views
Month 61: 27 views
Month 62: 25 views
Month 63: 22 views
Month 64: 39 views
Month 65: 31 views
Month 66: 22 views
Month 67: 36 views
Month 68: 29 views
Month 69: 26 views
Month 70: 27 views
Month 71: 35 views
Month 72: 18 views
Month 73: 32 views
Month 74: 15 views
Month 75: 22 views
Month 76: 23 views
Month 77: 41 views
Month 78: 32 views
Month 79: 17 views
Month 80: 39 views
Month 81: 26 views
Month 82: 43 views
Month 83: 39 views
Month 84: 28 views
Month 85: 25 views
Month 86: 35 views
Month 87: 18 views
Month 88: 31 views
Month 89: 36 views
Month 90: 39 views
Month 91: 22 views
Month 92: 15 views
Month 93: 25 views
Month 94: 24 views
Month 95: 33 views
Month 96: 30 views
Month 97: 24 views
Month 98: 26 views
Month 99: 37 views
Month 100: 47 views
Month 101: 26 views
Month 102: 25 views
Month 103: 30 views
Month 104: 26 views
Month 105: 36 views
Month 106: 25 views
Month 107: 28 views
Month 108: 49 views
Month 109: 27 views
Month 110: 37 views
Month 111: 19 views
Month 112: 35 views
Month 113: 21 views
Month 114: 21 views
Month 115: 21 views
Month 116: 34 views
Month 117: 45 views
Month 118: 21 views
Month 119: 40 views
Month 120: 16 views
Month 121: 41 views
Month 122: 36 views
Month 123: 42 views
Month 124: 37 views
Month 125: 40 views
Month 126: 27 views
Month 127: 45 views
Month 128: 32 views
Month 129: 41 views
Month 130: 32 views
Month 131: 25 views
Month 132: 20 views
Month 133: 34 views
Month 134: 24 views
Month 135: 33 views
Month 136: 36 views
Month 137: 35 views
Month 138: 48 views
Month 139: 61 views
Month 140: 27 views
Month 141: 21 views
Month 142: 40 views
Month 143: 33 views

Total Views: 4408

Total Downloads: 2190

2026 Trends

Published Article

Our website is actively being updated, and changes may occur frequently. Please clear your browser cache if needed. For feedback or error reporting, please email [email protected]