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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol
Toxicology and Applied Pharmacology, Volume 271, No. 1, Year 2013
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Description
Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1-1000. ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000. ng/ml (3.87. μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000. ng/ml (3.87. μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. © 2013 Elsevier Inc.
Authors & Co-Authors
Frizzell, Caroline
United Kingdom, Belfast
Queen's University Belfast
Ndossi, Doreen G.
Norway, As
Norges Miljø- og Biovitenskapelige Universitet
Tanzania, Morogoro
Sokoine University of Agriculture
Kalayou, Shewit T.
Norway, As
Norges Miljø- og Biovitenskapelige Universitet
Ethiopia, Makale
Mekelle University
Eriksen, Gunnar Sundstøl
Norway, Oslo
Veterinærinstituttet
Verhaegen, Steven
Norway, As
Norges Miljø- og Biovitenskapelige Universitet
Sörlie, Morten
Norway, As
Norges Miljø- og Biovitenskapelige Universitet
Elliott, Christopher T.
United Kingdom, Belfast
Queen's University Belfast
Ropstad, Erik
Norway, As
Norges Miljø- og Biovitenskapelige Universitet
Connolly, L.
United Kingdom, Belfast
Queen's University Belfast
Statistics
Citations: 63
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1016/j.taap.2013.05.002
ISSN:
0041008X
e-ISSN:
10960333
Research Areas
Cancer
Genetics And Genomics