Effects of Ivermectin Exposure on Regeneration ofD. dorotocephalaPlanaria: Exploiting Human‐Approved Ion Channel Drugs as Morphoceuticals

Abstract

Transformative applications in regenerative medicine await increased control of processes implementing repair and remodeling of complex living structures. Recent work reveals ion channel drugs as a powerful toolkit for modulating endogenous bioelectric circuits that control growth and form in vivo and in vitro. It is therefore especially important to develop assays in model systems that will enable the testing of these “morphoceuticals”—compounds with predictable effects on anatomical structure. The regenerative planaria are an ideal model system for this purpose. Several studies have shown a role for bioelectric signaling in planarian regeneration, but these have focused on Dugesia japonica and Schmidtea mediterranea. It is not known how the alterations of ion channel activity would affect regeneration in other species of planaria—an important aspect of building robust computational models of bioelectric circuits. Here, the effect of ivermectin (IVM), a chloride channel opener drug commonly used to combat heartworm is tested, on regeneration in a new species of planaria: Dugesia dorotocephala. Exposure to IVM during regeneration results in patterning abnormalities, such as bifurcated tails with partial heads, as well as delayed regeneration. These data extend our understanding of the effects of human‐approved ion channel drugs on regenerative processes.

Enzymatic decontamination of paraoxon-ethyl limits long-term effects in planarians

“…(B) Regeneration process monitoring for each condition: control conditions in water and enzyme solution, paraoxon-ethyl at 0.5 µM and its degradation product and paraoxon-ethyl at 5 µM and its degradation product. (2020) 10:3843 | https://doi.org/10.1038/s41598-020-60846-1 www.nature.com/scientificreports www.nature.com/scientificreports/ active ingredient of the widespread herbicide Roundup, have led to similar abnormalities in planarians in recent studies 42,43 . evaluation of behavioral disruptions in planarians.…”