Comparative toxicological prospection of carvacrol and its acetylated derivative in the zebrafish (Danio rerio) and human blood models

Abstract

The search for natural-based compounds presenting pesticide activity has intensified in the last decade. However, the lack of comparative toxicological studies is a limiting factor for their commercialization. The aim of this study was to compare the toxicity of carvacrol (natural), acetylcarvacrol (semi-synthetic), and fipronil (synthetic) employing two models: human blood and developing zebrafish (Danio rerio). A series of concentrations was used to evaluate the effects of these chemicals on hemolytic activity, erythrocyte morphology, leucocyte viability, and DNA fragmentation. In the zebrafish model, we assessed survivability, hatchability, malformations, morphometrics, behavior, mitochondrial bioenergetics, apoptosis, reactive oxygen species as well as gene expression. Our findings suggest that fipronil presents relatively high toxicity to human blood cells compared to the other chemicals. Carvacrol at high concentrations was also toxic, but its use at low concentrations as well as its acetylated derivative caused reduced damage to blood cells. In the zebrafish model, fipronil exhibited high acute toxicity following seven days of continuous exposure. It also affected the expression of genes related to mitochondrial activity, decreased swim bladder surface area, induced reactive oxygen species, and hypoactivity in the visual motor response test. Carvacrol and acetylcarvacrol were considerably less toxic to developing zebrafish compared to fipronil. Acetylation of carvacrol was also responsible for a reduction in lethality. Taken together, our results demonstrate that carvacrol and acetylcarvacrol have considerably reduced toxicity when compared to fipronil in the two models evaluated. Moreover, chemical modification of a natural compound such as carvacrol would seem to be a promising alternative to improve its biological activity and reduce its toxicity to non-target organisms.