Journal
CURRENT RESEARCH IN TOXICOLOGY
Volume 2, Issue -, Pages 386-398Publisher
ELSEVIER
DOI: 10.1016/j.crtox.2021.11.002
Keywords
Phenethylamines; Recreational drugs; DNA interaction; Malformation; Embryo mortality
Categories
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq/Brazil) [429121/2018-0]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/Brazil) [001, 88881.516313/2020-01]
- Fundacao de Amparo a Pesquisa do Estado de Alagoas (FAPEAL/Brazil) [60030 000863/2016]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG/Brazil) [RED-00042-16]
- CNPq/Brazil
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The toxicological effects of 25H-NBOMe and 25H-NBOH on zebrafish embryos and larvae were demonstrated, including both lethal and non-lethal effects. These drugs not only caused high embryo mortality, but also various malformations and adverse effects. In vitro experiments showed that the drugs have an affinity for DNA, leading to conformational changes in the DNA structure.
Toxicological effects of 25H-NBOMe and 25H-NBOH recreational drugs on zebrafish embryos and larvae at the end of 96 h exposure period were demonstrated. 25H-NBOH and 25H-NBOMe caused high embryo mortality at 80 and 100 pig mL(-1), respectively. According to the decrease in the concentration tested, lethality decreased while non-lethal effects were predominant up to 10 and 50 pig mL(-1) of 25H-NBOH and 25H-NBOMe, respectively, including spine malformation, egg hatching delay, body malformation, otolith malformation, pericardial edema, and blood clotting. We can disclose that these drugs have an affinity for DNA in vitro using biophysical spectroscopic assays and molecular modeling methods. The experiments demonstrated that 25H-NBOH and 25H-NBOMe bind to the unclassical major groove of ctDNA with a binding constant of 27.00 x 10(4) M-1 and 5.27 x 10(4) M-1, respectively. Furthermore, these interactions lead to conformational changes in the DNA structure. Therefore, the results observed in the zebrafish embryos and DNA may be correlated.
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