Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish

Abstract

The zebrafish fish embryo toxicity (FET) test is increasingly employed for alternative toxicity studies, yet our previous research identified increased sensitivity of zebrafish slightly older than embryos employed in FET methods (0-4 d postfertilization [dpf]). We identified rapid steady-state accumulation of diphenhydramine across zebrafish embryo and larval stages. However, significantly (p < 0.05) lower accumulation was observed at 48 h compared to 96 h in chorionated and dechorionated embryos (0-4 dpf), but not in zebrafish at 7 to 11 and 14 to 18 dpf. Increased uptake and toxicity of diphenhydramine was further observed in zebrafish at 7 to 11 and 14 to 18 dpf compared with 0-4 dpf embryos with chorion or dechorionated, which indicates that differential zebrafish sensitivity with age is associated with accumulation resulting from gill and other toxicokinetic and toxicodynamic changes during development. Environ Toxicol Chem 2018;37:1175-1181. © 2017 SETAC.

Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae

“…From that moment, instead of only transdermal or trans-gill absorption, the larvae will also ingest the exogenous compound orally. Recently examined absorption of the antihistamine diphenhydramine between zebrafish embryos and larvae showed an chorion-independent increase in absorption between 2 and 4 dpf and are in concordance with our results here 34 . The absorption rate constant did not increase further between 4 and 5 dpf, suggesting that potential other processes that add to the absorption of paracetamol, do not show maturational changes in the age range studied here.…”

Toward Less Hazardous Industrial Compounds: Coupling Quantum Mechanical Computations, Biomarker Responses, and Behavioral Profiles To Identify Bioactivity of SN2 Electrophiles in Alternative Vertebrate Models

“…It is important to note that we followed standardized OECD and EPA guidelines, in which zebrafish exposure was initiated 4–6 h post fertilization and fathead minnow larvae exposure began within 24 h posthatch, respectively, to maximize broader comparability of results presented here with other studies. In addition to influencing behavioral responses, the development age of fish can influence biotransformation, bioaccumulation, and toxicodynamics of various chemical contaminants. ,, Therefore, this study was not designed to directly examine whether differential behavioral response thresholds exhibited between larval zebrafish and fathead minnows are related to differences in age and/or species. However, observations in the present study indicate that larval zebrafish behaviors may provide greater diagnostic utility than larval fathead minnows for S N 2 and other electrophilic bioactivity.…”

Exploring the mechanisms of graphene oxide behavioral and morphological changes in zebrafish

“…Additionally, a progressive change in the chorion structure has been reported during embryonic development. In consequence, future studies are needed to understand chorionic influences on the uptake of chemicals ranging in molecular size and physicochemical properties among fish models (Kristofco et al 2018).…”