Effects of Five Substances with Different Modes of Action on Cathepsin H, C and L Activities in Zebrafish Embryos

Eberhard Küster, Stefan Kalkhof, Silke Aulhorn, Martin von Bergen and Ulrike Gündel
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Eberhard Küster: Department Bioanalytical Ecotoxicology, UFZ- Helmholtz -Centre for Environmental Research—UFZ, 04318 Leipzig, Germany
Stefan Kalkhof: Department of Molecular Systems Biology, UFZ- Helmholtz -Centre for Environmental Research—UFZ, 04318 Leipzig, Germany
Silke Aulhorn: Department Bioanalytical Ecotoxicology, UFZ- Helmholtz -Centre for Environmental Research—UFZ, 04318 Leipzig, Germany
Martin von Bergen: Department of Molecular Systems Biology, UFZ- Helmholtz -Centre for Environmental Research—UFZ, 04318 Leipzig, Germany
Ulrike Gündel: Department Bioanalytical Ecotoxicology, UFZ- Helmholtz -Centre for Environmental Research—UFZ, 04318 Leipzig, Germany

IJERPH, 2019, vol. 16, issue 20, 1-15

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 LC 50 (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.

Keywords: vitellogenin (Vtg); toxicity; risk assessment; 3R animal test replacement method; cysteine protease (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:16:y:2019:i:20:p:3956-:d:277531

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