A versatile toxicity evaluation of ethyl carbamate (urethane) on zebrafish embryos: Morphological, physiological, histopathological, immunohistochemical, transcriptional and behavioral approaches

Toxicol Lett. 2021 Dec 15:353:71-78. doi: 10.1016/j.toxlet.2021.09.012. Epub 2021 Oct 1.

Abstract

Ethyl carbamate (EC, urethane), which is used as an anesthetic especially by veterinarians due to its very long duration of action, is also a naturally occurring compound in all fermented foods and beverages. Although the health problem of EC is related to its carcinogenic potential, the scarcity of current studies that can be used in the evaluation of usage limits encouraged us to do this study. In this context, zebrafish embryos were exposed to serial doses of EC. According to the results, it was observed that EC exposure caused a significant decrease in survival and hatching rates as well as significant body malformations. Whole-mount staining results showed that EC caused dose-dependent increased apoptosis. Oxidative stress caused by EC exposure was demonstrated by whole-mount staining, transcriptional and immunohistochemically. Furthermore, it has been shown histochemically that EC exposure causes necrosis and degeneration in the brain. In behavioral tests, it was observed that EC caused hyperactivity associated with these neuronal degenerations. In addition, a dramatic decrease in blood flow was detected in association with pericardial edema. In the light of the current results, it should be carefully considered that EC can be found naturally in many human diets, especially fermented foods.

Keywords: 8 OHdG; Caspase 3; Fermented foods; Hyperactivity; Zebrafish.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / abnormalities
  • Embryo, Nonmammalian / drug effects*
  • Gene Expression Regulation, Developmental / drug effects*
  • Immunohistochemistry
  • Larva / drug effects
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic
  • Urethane / administration & dosage
  • Urethane / toxicity*
  • Zebrafish

Substances

  • Reactive Oxygen Species
  • Urethane