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

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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84616
Date06 April 2023
CreatorsKüster, Eberhard, Kalkhof, Stefan, Aulhorn, Silke, von Bergen, Martin, Gündel, Ulrike
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation1661-7827, 3956

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