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Studies on the metabolism of ochratoxin A / Maria Aletta StanderStander, Maria Aletta January 1999 (has links)
The ochratoxins, metabolites of certain Aspergillus and Penicillium species are the first group
of mycotoxins discovered subsequent to the epoch-making discovery of the aflatoxins.
Ochratoxin A (OTA) is a very important mycotoxin owing to its frequent occurrence in
nature, its established role in Danish porcine nephropathy and in poultry mycotoxicoses and
its implicated role in Balkan endemic nephropathy and urinary system tumors among
population groups in North Africa. Chapters 2 and 3 highlight the importance of OTA and
the research currently being done on mycotoxins. These efforts are focused on the molecular
genetics of toxinogenic fungi; the mechanism of their action; species differences in
metabolism and pharmacokinetics; quantification of mycotoxins; risk assessments on the
exposure of man and animals to mycotoxins and regulations for the control of mycotoxin
contamination.
Methods developed to analyse OTA in different matrices by using reversed phase high
performance-liquid chromatography with fluorescence detection and tandem liquid
chromatography-mass spectrometry techniques are described in Chapter 10. Amino propyl
solid phase extraction columns were used for the first time in cleanup steps of ochratoxin
analysis. These techniques and methods were applied to the first survey on the levels of OTA
in coffee on the South African retail market (Chapter 5). The results suggest that the levels
of OT A in the coffee on the South African market are somewhat higher than the levels of
OTA in coffees on the European market.
The possibility to biologically produce different halogen-ochratoxins by supplementing the
growth medium of Aspergillus ochraceus with halogen salts was investigated. Bromoochratoxin
A was produced for the first time in this way. Supplementation of inoculated
wheat with potassium iodide and -fluoride resulted in the poisoning of the yeast and no iodoor
fluoro-ochratoxin B was produced. It was found that Aspergillus ochraceus produced OTA
in higher yields at elevated levels of potassium chloride. This finding has important
commercial applications in the production ofOTA (Chapter 4).
The ochratoxins are hydrolyzed in vivo by carboxypeptidase A. The hydrolysis of the
ochratoxins and analogues by carboxypeptidase A was measured in vitro in a structurefunction
relation study by employing mass spectrometric techniques. The kinetic data of the
ochratoxins were compared to the values of a number of synthesized structural analogues. It
was found that the halogen containing analogues had lower turnovers than their des-halo
analogues. There were no substantial differences in the kinetic data between the different
halogen containing analogues (Chapter 8).
The toxicokinetics of OTA in vervet monkeys were determined for the first time. The
clearance of OTA from the plasma suggested a two-compartment model and the elimination
half-life was determined to be 19-21 days. The half-life of OTA in humans was determined
by allometric calculations to be 46 days. We came to the conclusion that the long term
consumption of OT A contaminated foods will lead to potentially hazardous levels of the toxin
in the body (Chapter 9). This hypothesis can be substantiated by the incidence of OTA in the
blood of various population groups.
Possible ways to decontaminate OT A contaminated foods by degrading the compound
biologically with yeast; moulds or lipases to non-toxic compounds were investigated. Eight
moulds, 323 yeasts and 23 lipases were screened for ochratoxin degradation. A lipase from
Aspergillus niger is the first lipase that was proven to degrade OTA (Chapter 7). Four yeasts
were found to degrade OT A of which one, Trichosporon mucoides degraded OTA
substantially within 48 hours in a growing culture (Chapter 6). In addition to this first report
of yeasts which have the ability to degrade OTA, the fungi Cochliobolus sativus, Penicillium
islandicum and Metarhizium anispoliae also proved to degrade OT A. OT A was degraded in
all instances to the non-toxic ochratoxin a and the amino acid phenylalanine. / Thesis (PhD (Chemistry))--Potchefstroom University for Christian Higher Education, 2000
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2 |
Studies on the metabolism of ochratoxin A / Maria Aletta StanderStander, Maria Aletta January 1999 (has links)
The ochratoxins, metabolites of certain Aspergillus and Penicillium species are the first group
of mycotoxins discovered subsequent to the epoch-making discovery of the aflatoxins.
Ochratoxin A (OTA) is a very important mycotoxin owing to its frequent occurrence in
nature, its established role in Danish porcine nephropathy and in poultry mycotoxicoses and
its implicated role in Balkan endemic nephropathy and urinary system tumors among
population groups in North Africa. Chapters 2 and 3 highlight the importance of OTA and
the research currently being done on mycotoxins. These efforts are focused on the molecular
genetics of toxinogenic fungi; the mechanism of their action; species differences in
metabolism and pharmacokinetics; quantification of mycotoxins; risk assessments on the
exposure of man and animals to mycotoxins and regulations for the control of mycotoxin
contamination.
Methods developed to analyse OTA in different matrices by using reversed phase high
performance-liquid chromatography with fluorescence detection and tandem liquid
chromatography-mass spectrometry techniques are described in Chapter 10. Amino propyl
solid phase extraction columns were used for the first time in cleanup steps of ochratoxin
analysis. These techniques and methods were applied to the first survey on the levels of OTA
in coffee on the South African retail market (Chapter 5). The results suggest that the levels
of OT A in the coffee on the South African market are somewhat higher than the levels of
OTA in coffees on the European market.
The possibility to biologically produce different halogen-ochratoxins by supplementing the
growth medium of Aspergillus ochraceus with halogen salts was investigated. Bromoochratoxin
A was produced for the first time in this way. Supplementation of inoculated
wheat with potassium iodide and -fluoride resulted in the poisoning of the yeast and no iodoor
fluoro-ochratoxin B was produced. It was found that Aspergillus ochraceus produced OTA
in higher yields at elevated levels of potassium chloride. This finding has important
commercial applications in the production ofOTA (Chapter 4).
The ochratoxins are hydrolyzed in vivo by carboxypeptidase A. The hydrolysis of the
ochratoxins and analogues by carboxypeptidase A was measured in vitro in a structurefunction
relation study by employing mass spectrometric techniques. The kinetic data of the
ochratoxins were compared to the values of a number of synthesized structural analogues. It
was found that the halogen containing analogues had lower turnovers than their des-halo
analogues. There were no substantial differences in the kinetic data between the different
halogen containing analogues (Chapter 8).
The toxicokinetics of OTA in vervet monkeys were determined for the first time. The
clearance of OTA from the plasma suggested a two-compartment model and the elimination
half-life was determined to be 19-21 days. The half-life of OTA in humans was determined
by allometric calculations to be 46 days. We came to the conclusion that the long term
consumption of OT A contaminated foods will lead to potentially hazardous levels of the toxin
in the body (Chapter 9). This hypothesis can be substantiated by the incidence of OTA in the
blood of various population groups.
Possible ways to decontaminate OT A contaminated foods by degrading the compound
biologically with yeast; moulds or lipases to non-toxic compounds were investigated. Eight
moulds, 323 yeasts and 23 lipases were screened for ochratoxin degradation. A lipase from
Aspergillus niger is the first lipase that was proven to degrade OTA (Chapter 7). Four yeasts
were found to degrade OT A of which one, Trichosporon mucoides degraded OTA
substantially within 48 hours in a growing culture (Chapter 6). In addition to this first report
of yeasts which have the ability to degrade OTA, the fungi Cochliobolus sativus, Penicillium
islandicum and Metarhizium anispoliae also proved to degrade OT A. OT A was degraded in
all instances to the non-toxic ochratoxin a and the amino acid phenylalanine. / Thesis (PhD (Chemistry))--Potchefstroom University for Christian Higher Education, 2000
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