Molecular signatures of angiogenesis inhibitors: a single-embryo untargeted metabolomics approach in zebrafish

• DOI: 10.1007/s00204-023-03655-5
• Publication Date: 2024-01-29T11:02:31Z
• Authors: Pia Wilhelmi; Volker Haake; Franziska M. Zick...; Varun Giri; Philipp Ternes; Peter Driemert; Julia Nöth; Stefan Scholz; Marta Barenys; Burkhard Flick; Barbara Birk; Hennicke Kamp; Robert Landsiedel; Dorothee Funk-Weyer
• Keywords: Developmental toxicity; Metabolome

Abstract Angiogenesis is a key process in embryonic development, disruption of this can lead to severe developmental defects, such as limb malformations. The identification molecular perturbations representative antiangiogenesis zebrafish embryo (ZFE) may guide the assessment toxicity from an endpoint- mechanism-based approach, thereby improving extrapolation findings humans. Thus, aim study was discover changes characteristic and toxicity. We exposed ZFEs two antiangiogenic drugs (SU4312, sorafenib) toxicants (methotrexate, rotenone) with putative action. Molecular were measured by performing untargeted metabolomics single embryos. metabolome response accompanied occurrence morphological alterations. Two distinct metabolic effect patterns observed. first pattern comprised common effects specific angiogenesis inhibitors known teratogen methotrexate, strongly suggesting shared mode action second involved joint methotrexate rotenone, likely related disturbances energy metabolism. metabolites pattern, phosphatidylserines, pterines, retinol, or coenzyme Q precursors, represented potential links contribute biomarker for toxicological testing.