2026/03/01 by Tanner F. Robertson, Adam Horn, Frances M. Smith +1 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Veterinary · #Immune Response and Inflammation #Veterinary Pharmacology and Anesthesia #Zebrafish Biomedical Research Applications
paper · pdf · doi:10.1242/dmm.052600
openalex publication_date 2026/03/01 · openalex created_date 2026/03/07 · openalex updated_date 2026/08/01
The veterinary sedative and alpha-2 adrenergic receptor (α2AR) agonist xylazine, found in the illicit opioid supply, is associated with cutaneous wounds in humans. Here, we developed a larval zebrafish model of xylazine-induced tissue damage to investigate the mechanisms by which xylazine affects the skin. Xylazine treatment caused keratinocyte extrusion, tissue-wide skin contraction and disruption of basal keratinocyte cell-cell interactions in zebrafish larvae. Notably, other α2AR agonists did not recapitulate most of these effects. Xylazine was recently described as a kappa opioid receptor (κOR) agonist, and we found that both xylazine and a separate κOR agonist acted directly on epithelial cells to drive cellular contraction and disrupt tissue homeostasis. Our model suggests that xylazine disrupts skin homeostasis through a direct mechanism involving epithelial cells and κOR, which may be of importance for the treatment of these wounds.