Abstract:
Diplodiosis, a neuromycotoxicosis of cattle and sheep grazing on mouldy cobs infected by
Stenocarpella maydis, is considered the last major veterinary mycotoxicosis for which the
causative mycotoxin is still unknown. The current study was aimed at characterizing the cell
death observed in mouse neuroblastoma (Neuro-2a), Chinese hamster ovary (CHO-K1) and
Madin–Darby bovine kidney (MDBK) cell lines exposed to the S. maydis metabolites (i.e.
diplodiatoxin and dipmatol) by investigating the roles of necrosis and apoptosis. Necrosis
was investigated using the lactate dehydrogenase (LDH) leakage and propidium iodide (PI)
flow cytometry assays and apoptosis was evaluated using the caspase-3/7 and Annexin V
flow cytometry assays. In addition, transmission electron microscopy (TEM) was used to
correlate the cell death pathways observed in this study with their typical morphologies. Both
diplodiatoxin and dipmatol (750 μM) induced necrosis and caspase-dependent apoptosis in
Neuro-2a, CHO-K1 and MDBK cells. Ultrastructurally, the two mycotoxins induced
mitochondrial damage, cytoplasmic vacuolation and nuclear fragmentation in the three cell
lines. These findings have laid a foundation for future studies aimed at elucidating in detail
the mechanism of action of the S. maydis metabolites.
