Universität zu Köln

Chaudhari, Umesh ORCID: 0000-0002-7743-4371, Nemade, Harshal, Sureshkumar, Poornima, Vinken, Mathieu ORCID: 0000-0001-5115-8893, Ates, Gamze ORCID: 0000-0002-9323-3465, Rogiers, Vera ORCID: 0000-0003-0635-7740, Hescheler, Juergen, Hengstler, Jan Georg and Sachinidis, Agapios (2018). Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch. Toxicol., 92 (1). S. 371 - 382. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-0738

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Abstract

There is a large demand of a human relevant in vitro test system suitable for assessing the cardiotoxic potential of cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an in vitro cardiotoxicity assay and identified genomic biomarkers of anthracycline-induced cardiotoxicity in our previous work. Here, five cosmetic ingredients were studied by the new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), and basic red 51 (BR51) based on cytotoxicity as well as ATP assays, beating rate, and genomic biomarkers to determine the lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC). The LOEC for beating rate were 400, 10, 3, >400, and 3 mu M for KJA, TS, TCC, NPT, and BR51, respectively. The corresponding concentrations for cytotoxicity or ATP depletion were similar, with the exception of TS and TCC, where the cardiomyo-cyte-beating assay showed positive results at non-cytotoxic concentrations. Functional analysis also showed that the individual compounds caused different effects on hiPSC-CMs. While exposure to KJA, TS, TCC, and BR51 induced significant arrhythmic beating, NPT slightly decreased cell viability, but did not influence beating. Gene expression studies showed that TS and NPT caused down-regulation of cytoskeletal and cardiac ion homeostasis genes. Moreover, TS and NPT deregulated genomic biomarkers known to be affected also by anthracyclines. The present study demonstrates that hiPSC-CMs can be used to determine LOECs and NOECs in vitro, which can be compared to human blood concentrations to determine margins of exposure. Our in vitro assay, which so far has been tested with several anthracyclines and cosmetics, still requires validation by larger numbers of positive and negative controls, before it can be recommended for routine analysis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chaudhari, Umesh UNSPECIFIED orcid.org/0000-0002-7743-4371 UNSPECIFIED Nemade, Harshal UNSPECIFIED UNSPECIFIED UNSPECIFIED Sureshkumar, Poornima UNSPECIFIED UNSPECIFIED UNSPECIFIED Vinken, Mathieu UNSPECIFIED orcid.org/0000-0001-5115-8893 UNSPECIFIED Ates, Gamze UNSPECIFIED orcid.org/0000-0002-9323-3465 UNSPECIFIED Rogiers, Vera UNSPECIFIED orcid.org/0000-0003-0635-7740 UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hengstler, Jan Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204444
DOI:	10.1007/s00204-017-2065-z
Journal or Publication Title:	Arch. Toxicol.
Volume:	92
Number:	1
Page Range:	S. 371 - 382
Date:	2018
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1432-0738
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HAIR DYE; TRICLOSAN; ZEBRAFISH; TOXICITY; DYNAMICS; ACID Multiple languages Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20444