Document Detail


Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture.
MedLine Citation:
PMID:  17825972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
At the level of the whole animal, the toxic effects of the mycotoxin deoxynivalenol (DON) range from causing diarrhoea, vomiting, gastro-intestinal inflammation to necrosis of several tissues. It also affects the immune system and leads to kidney lesions. Although DON has been tested in different human and animal cell lines for its cytotoxicity, these tests might be limited due to the disadvantages of cell lines (e.g. immortalization, tumour derivation, longtime cultivation) and do not necessarily reflect the response of normal cells. In order to overcome this problem and to be closer to the human situation, we studied the effect of DON in human kidney epithelial cells (renal proximal tubule epithelial cells, RPTEC) and human lung fibroblasts (normal human lung fibroblast, NHLF) in primary culture. Cell viability, apoptotic and necrotic cell death, collagens I, III and IV as well as fibronectin secretion were determined. It could be demonstrated that DON has a distinct cytotoxic effect on human primary cells. A reduction in viability can be observed in both cell types, with fibroblasts reacting more sensitive. Furthermore, DON caused mainly necrotic cell death in kidney cells whereas mainly apoptotic cell death in fibroblasts. DON had no effect on collagen secretion in RPTEC cells. Collagen secretion was partially decreased in NHLF. In both cells, fibronectin secretion was reduced after 5 days of exposure. We also studied the metabolism and the cellular uptake of DON using LC-MS/MS. DON was neither metabolized by proximal tubule cells nor by fibroblasts. DON is incorporated into the cells whereas the intracellular amount of DON in kidney cells is higher than in fibroblasts. No accumulation of DON occurred in the cells.
Authors:
Maika Königs; Marlies Lenczyk; Gerald Schwerdt; Hildegard Holzinger; Michael Gekle; Hans-Ulrich Humpf
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-01
Journal Detail:
Title:  Toxicology     Volume:  240     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2007-11-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  48-59     Citation Subset:  IM    
Affiliation:
Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, 48149 Münster, Germany.
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MeSH Terms
Descriptor/Qualifier:
Caspase 3 / metabolism
Cell Count
Cell Survival / drug effects
Cells, Cultured
Collagen / metabolism
Epithelial Cells / drug effects*,  metabolism,  pathology
Fibroblasts / drug effects*,  metabolism,  pathology
Fibronectins / metabolism
Humans
Kidney Tubules, Proximal* / drug effects,  metabolism,  pathology
Lung* / drug effects,  metabolism,  pathology
Microscopy, Fluorescence
Necrosis
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Trichothecenes* / pharmacokinetics,  toxicity
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Trichothecenes; 51481-10-8/deoxynivalenol; 9007-34-5/Collagen; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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