Fig 1.
Biochemical changes that occur in a dying cell with disrupted osmoregulation.
It is believed that hydropic drugs might inactivate the Na+/K+ antiporter pump or alternatively lead to decreased ATP production, ultimately leading to accumulation of Na+, Ca2+, and water and effluxes of K+ and Mg2+. A decreased Mg2+ level also suggests impaired functioning of the Na+/K+ pump. The drug might cause a rapid influx of water by an as of yet unknown mechanism, causing organelles (vacuoles, Golgi bodies, mitochondria, and rough endoplasmic reticulum) to dilate extensively and disrupting normal biological functioning. Water-filled vacuoles tend to fuse to form giant vacuoles that subsequently rupture and kill cells. Contrariwise, mitochondrial damage might also be a factor for decreased ATP production in the cell. The dashed lines (red or black) indicate uncharacterized sections of the pathway, while solid lines (black) represent regular biological attributes. ATP, adenosine triphosphate; ER, endoplasmic reticulum; ROS, reactive oxygen species.
Fig 2.
Sequence of vacuolar cell death in parasitic nematodes.
Hydropic anthelmintics, such as 5-iodoindole, disrupt osmoregulation causing rapid water influx into nematodes. This leads to the formation of multiple vacuoles. Depending on the severity of the injury or chemical dosages, injury due to vacuolization can be classified as reversible (where the nematodes can be revived back to life) or irreversible (where the nematodes pass the point of no return, causing them to die). ATP, adenosine triphosphate. The phenotypes were re-constructed by adopting images and concepts from our previous publications [12, 14].
Table 1.
Chemicals that trigger vacuole formation in parasitic nematodes.