Effects of the mycotoxin deoxynivalenol on human primary hepatocytes.
Toxic effects of the mycotoxin deoxynivalenol (DON) observed in animals range from diarrhea, vomiting, gastro-intestinal inflammation to necrosis of several tissues. In the last years, DON has been tested in hepatocytes of several animal species for its cytotoxicity. However, these tests are limited to the use of animal cells. No studies using human hepatocytes are available. Further investigations with the human hepatocellular liver carcinoma cell line HepG2 might be limited due to the disadvantages of cell lines (e. g. immortalization, tumor derivation, longtime cultivation) and do not necessarily reflect the response of normal human cells. In order to overcome this problem and to be closer to the human situation, we studied the effect of DON in human primary hepatocytes and compared these data to the effects in the HepG2 cell line. Cell viability, apoptotic and necrotic cell death, albumin secretion and metabolic activity were determined. It could be demonstrated that DON has a distinct cytotoxic effect on human primary hepatocytes. Viability, protein content and albumin secretion were reduced in a dose-dependent manner. The apoptotic key enzyme caspase-3 was activated, while LDH release occurred only after long incubation time due to a secondary necrosis. Furthermore, we studied the metabolism of DON using LC-MS/MS. DON was neither metabolized by primary hepatocytes cells nor by the HepG2 cell line.
Königs
Maika
M
Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Germany.
Schwerdt
Gerald
G
Gekle
Michael
M
Humpf
Hans-Ulrich
HU
D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D005562:Formazans / Q000032:analysis; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D021241:Spectrometry, Mass, Electrospray Ionization; D014255:Trichothecenes / Q000633:toxicity*
D005562:Formazans; D009183:Mycotoxins; D014255:Trichothecenes; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; C007262:deoxynivalenol