Evaluation of the potential of Xenopus laevis as a novel model organism for the detection of drug-induced cardiotoxicity

Wyville, Saskia (2025) Evaluation of the potential of Xenopus laevis as a novel model organism for the detection of drug-induced cardiotoxicity. Doctoral thesis, University of East Anglia.

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Abstract

As animal use in science decreases the need for models to accurately predict drug-induced cardiotoxicity increases. Xenopus laevis embryos provide the potential for initial molecule screening on a medium- to high-throughput scale, allowing toxic molecules to be removed earlier in development, reducing the number and expense of later mammalian trials.

To investigate X. laevis models two factors were examined- the effect on heart rate and the detection or change in expression of miRNA biomarkers. To determine heart rate, embryos were treated with known cardiotoxic drugs such as doxorubicin and terfenadine at a range of concentrations at NF stage 38 and grown in drug-containing media until NF stage 45 before being anaesthetised and imaged. Video footage was used to determine heart rate through movement of blood between heart chambers and a novel program in R Studio. Biomarkers from the literature that indicated cardiotoxicity, miRNA-208, miRNA-499, and miRNA-143 were used. Embryos were exposed in the same manner until NF stage 45, before being harvested into ‘head’ and ‘tail’ samples; with head sample containing the heart and major organs and tail sample containing highly vascular tail tissue, before being assessed using qRT-PCR to determine expression levels of target miRNAs.

When exposed to doxorubicin and terfenadine, heart rate decreased and incidence of arrhythmia increased at the higher concentrations of the drug, mirroring the effects seen in mammalian models of cardiotoxicity. The qRTPCR results were varied, with strong indications of increasing expression of miRNA-499 and miRNA-143 in the embryos exposed to the highest concentrations of terfenadine, and a reduction in expression of miRNA-499 and miRNA-143 in embryos exposed to the highest concentrations of doxorubicin.

The results obtained in this study indicate that X. Laevis would make a suitable model for assessing drug-induced cardiotoxicity and the methodologies employed lend themselves well to scaling for industrial applications.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	10 Nov 2025 11:18
Last Modified:	10 Nov 2025 11:18
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100936
DOI:

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