Acute toxicities of fluorene, fluorene-1-carboxylic acid, and fluorene-9-carboxylic acid on zebrafish embryos (Danio rerio): Molecular mechanisms of developmental toxicities of fluorene-1-carboxylic acid

Abstract

In this study, fluorene (FL), FL-1-carboxylic acid (FC-1), and FL-9-carboxylic acid (FC-9) were investigated to understand their acute toxicity by measuring inhibitory effects on hatching rates and developmental processes of zebrafish embryos (Danio rerio). For exposure concentrations up to 3000 μg/L, FC-1 alone showed acute toxicity at 1458 μg/L for LC₅₀ value. FC-1 caused yolk sac and spinal deformities, and pericardial edema. Molecular studies were undertaken to understand FC-1 toxicity examining 61 genes after exposure to 5 μM (equivalent to LC₂₀ value of FC-1) in embryos. In the FC-1-treated embryos, the expression of the cyp7a1 gene, involved in bile acid biosynthesis, was dramatically decreased, while the expression of the Il-1β gene involved in inflammation was remarkably increased. In addition to these findings, in FC-1-treated embryos, the expression of nppa gene related to the differentiation of the myocardium was 3-fold increased. On the other hand, cyp1a, cyp3a, ugt1a1, abcc4, mdr1, and sult1st1 responsible for detoxification of xenobiotics were upregulated in FC-9-treated embryos. Taken together, carboxylation on carbon 1 of FL increased acute toxicity in zebrafish embryos, and its toxicity might be related to morphological changes with modification of normal biological functions and lowered defense ability.

Keywords: Bile acid production; Fluorene-1-carboxylic acid; Heart development; Pericardial edema; Yolk sac and spinal deformity.