Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.3390/ijerph16203956
Lizenz creative commons licence
Titel (primär) Effects of five substances with different modes of action on cathepsin H, C and L activities in zebrafish embryos
Autor Küster, E. ORCID logo ; Kalkhof, S.; Aulhorn, S.; von Bergen, M.; Gündel, U.
Journal / Serie International Journal of Environmental Research and Public Health
Erscheinungsjahr 2019
Band/Volume 16
Heft 20
Seite von art. 3956
Sprache englisch
Keywords vitellogenin (Vtg); toxicity; risk assessment; 3R animal test replacement method; cysteine protease
Abstract Cathepsins have been proposed as biomarkers of chemical exposure in the zebrafish embryo model but it is unclear whether they can also be used to detect sublethal stress. The present study evaluates three cathepsin types as candidate biomarkers in zebrafish embryos. In addition to other functions, cathepsins are also involved in yolk lysosomal processes for the internal nutrition of embryos of oviparous animals until external feeding starts. The baseline enzyme activity of cathepsin types H, C and L during the embryonic development of zebrafish in the first 96 h post fertilisation was studied. Secondly, the effect of leupeptin, a known cathepsin inhibitor, and four embryotoxic xenobiotic compounds with different modes of action (phenanthrene—baseline toxicity; rotenone—an inhibitor of electron transport chain in mitochondria; DNOC (Dinitro-ortho-cresol)—an inhibitor of ATP synthesis; and tebuconazole—a sterol biosynthesis inhibitor) on in vivo cathepsin H, C and L total activities have been tested. The positive control leupeptin showed effects on cathepsin L at a 20-fold lower concentration compared to the respective LC50 (0.4 mM) of the zebrafish embryo assay (FET). The observed effects on the enzyme activity of the four other xenobiotics were not or just slightly more sensitive (factor of 1.5 to 3), but the differences did not reach statistical significance. Results of this study indicate that the analysed cathepsins are not susceptible to toxins other than the known peptide-like inhibitors. However, specific cathepsin inhibitors might be identified using the zebrafish embryo.
dauerhafte UFZ-Verlinkung
Küster, E., Kalkhof, S., Aulhorn, S., von Bergen, M., Gündel, U. (2019):
Effects of five substances with different modes of action on cathepsin H, C and L activities in zebrafish embryos
Int. J. Environ. Res. Public Health 16 (20), art. 3956