In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay
The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay t...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
[1. September 2022]
|
| In: |
Toxicology letters
Year: 2022, Jahrgang: 368, Pages: 33-46 |
| ISSN: | 1879-3169 |
| DOI: | 10.1016/j.toxlet.2022.08.006 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.toxlet.2022.08.006 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0378427422009869 
|
| Verfasserangaben: | Tim Brecklinghaus, Wiebke Albrecht, Julia Duda, Franziska Kappenberg, Lisa Gründler, Karolina Edlund, Rosemarie Marchan, Ahmed Ghallab, Cristina Cadenas, Adrian Rieck, Nachiket Vartak, Laia Tolosa, José V. Castell, Iain Gardner, Emina Halilbasic, Michael Trauner, Anett Ullrich, Anja Zeigerer, Özlem Demirci Turgunbayer, Georg Damm, Daniel Seehofer, Jörg Rahnenführer, Jan G. Hengstler |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1822645956 | ||
| 003 | DE-627 | ||
| 005 | 20230427160535.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 221116s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.toxlet.2022.08.006 |2 doi | |
| 035 | |a (DE-627)1822645956 | ||
| 035 | |a (DE-599)KXP1822645956 | ||
| 035 | |a (OCoLC)1361692166 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Brecklinghaus, Tim |d 1992- |e VerfasserIn |0 (DE-588)119841703X |0 (DE-627)1680797484 |4 aut | |
| 245 | 1 | 0 | |a In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay |c Tim Brecklinghaus, Wiebke Albrecht, Julia Duda, Franziska Kappenberg, Lisa Gründler, Karolina Edlund, Rosemarie Marchan, Ahmed Ghallab, Cristina Cadenas, Adrian Rieck, Nachiket Vartak, Laia Tolosa, José V. Castell, Iain Gardner, Emina Halilbasic, Michael Trauner, Anett Ullrich, Anja Zeigerer, Özlem Demirci Turgunbayer, Georg Damm, Daniel Seehofer, Jörg Rahnenführer, Jan G. Hengstler |
| 264 | 1 | |c [1. September 2022] | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 16.112022 | ||
| 520 | |a The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds. | ||
| 650 | 4 | |a Alternative methods | |
| 650 | 4 | |a DILI | |
| 650 | 4 | |a Lipid droplets | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a Steatosis | |
| 700 | 1 | |a Albrecht, Wiebke |e VerfasserIn |4 aut | |
| 700 | 1 | |a Duda, Julia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kappenberg, Franziska |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gründler, Lisa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Edlund, Karolina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Marchan, Rosemarie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ghallab, Ahmed |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cadenas, Cristina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rieck, Adrian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vartak, Nachiket |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tolosa, Laia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Castell, José V. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gardner, Iain |e VerfasserIn |4 aut | |
| 700 | 1 | |a Halilbasic, Emina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trauner, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ullrich, Anett |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zeigerer, Anja |e VerfasserIn |0 (DE-588)1208340778 |0 (DE-627)1694605566 |4 aut | |
| 700 | 1 | |a Demirci Turgunbayer, Özlem |e VerfasserIn |4 aut | |
| 700 | 1 | |a Damm, Georg |e VerfasserIn |4 aut | |
| 700 | 1 | |a Seehofer, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rahnenführer, Jörg |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hengstler, Jan G. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Toxicology letters |d Amsterdam [u.a.] : Elsevier Science, 1977 |g 368(2022) vom: Sept., Seite 33-46 |h Online-Ressource |w (DE-627)306710862 |w (DE-600)1500784-4 |w (DE-576)08243607X |x 1879-3169 |7 nnas |a In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay |
| 773 | 1 | 8 | |g volume:368 |g year:2022 |g month:09 |g pages:33-46 |g extent:14 |a In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.toxlet.2022.08.006 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0378427422009869 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20221116 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 1208340778 |a Zeigerer, Anja |m 1208340778:Zeigerer, Anja |p 18 | ||
| 999 | |a KXP-PPN1822645956 |e 4212265672 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Gesehen am 16.112022"],"language":["eng"],"recId":"1822645956","title":[{"title_sort":"In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay","title":"In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay"}],"person":[{"role":"aut","display":"Brecklinghaus, Tim","roleDisplay":"VerfasserIn","given":"Tim","family":"Brecklinghaus"},{"given":"Wiebke","family":"Albrecht","role":"aut","display":"Albrecht, Wiebke","roleDisplay":"VerfasserIn"},{"family":"Duda","given":"Julia","display":"Duda, Julia","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Kappenberg","given":"Franziska","roleDisplay":"VerfasserIn","display":"Kappenberg, Franziska","role":"aut"},{"given":"Lisa","family":"Gründler","role":"aut","display":"Gründler, Lisa","roleDisplay":"VerfasserIn"},{"display":"Edlund, Karolina","roleDisplay":"VerfasserIn","role":"aut","family":"Edlund","given":"Karolina"},{"role":"aut","display":"Marchan, Rosemarie","roleDisplay":"VerfasserIn","given":"Rosemarie","family":"Marchan"},{"family":"Ghallab","given":"Ahmed","display":"Ghallab, Ahmed","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Cadenas, Cristina","role":"aut","family":"Cadenas","given":"Cristina"},{"given":"Adrian","family":"Rieck","role":"aut","display":"Rieck, Adrian","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Vartak, Nachiket","role":"aut","family":"Vartak","given":"Nachiket"},{"family":"Tolosa","given":"Laia","display":"Tolosa, Laia","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Castell","given":"José V.","roleDisplay":"VerfasserIn","display":"Castell, José V.","role":"aut"},{"given":"Iain","family":"Gardner","role":"aut","display":"Gardner, Iain","roleDisplay":"VerfasserIn"},{"given":"Emina","family":"Halilbasic","role":"aut","roleDisplay":"VerfasserIn","display":"Halilbasic, Emina"},{"given":"Michael","family":"Trauner","role":"aut","display":"Trauner, Michael","roleDisplay":"VerfasserIn"},{"family":"Ullrich","given":"Anett","display":"Ullrich, Anett","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Zeigerer, Anja","given":"Anja","family":"Zeigerer"},{"given":"Özlem","family":"Demirci Turgunbayer","role":"aut","roleDisplay":"VerfasserIn","display":"Demirci Turgunbayer, Özlem"},{"display":"Damm, Georg","roleDisplay":"VerfasserIn","role":"aut","family":"Damm","given":"Georg"},{"display":"Seehofer, Daniel","roleDisplay":"VerfasserIn","role":"aut","family":"Seehofer","given":"Daniel"},{"given":"Jörg","family":"Rahnenführer","role":"aut","roleDisplay":"VerfasserIn","display":"Rahnenführer, Jörg"},{"roleDisplay":"VerfasserIn","display":"Hengstler, Jan G.","role":"aut","family":"Hengstler","given":"Jan G."}],"physDesc":[{"extent":"14 S."}],"relHost":[{"id":{"eki":["306710862"],"zdb":["1500784-4"],"issn":["1879-3169"]},"origin":[{"publisherPlace":"Amsterdam [u.a.]","dateIssuedDisp":"1977-","dateIssuedKey":"1977","publisher":"Elsevier Science"}],"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"Toxicology letters","subtitle":"an international journal for the rapid publication of short reports on all aspects of toxicology especially mechanisms of toxicity","title_sort":"Toxicology letters"}],"part":{"text":"368(2022) vom: Sept., Seite 33-46","volume":"368","extent":"14","year":"2022","pages":"33-46"},"pubHistory":["1.1977 -"],"recId":"306710862","language":["eng"],"type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 27.07.2020","Ungezählte Beil.: Supplement"],"disp":"In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assayToxicology letters"}],"origin":[{"dateIssuedDisp":"[1. September 2022]","dateIssuedKey":"2022"}],"id":{"doi":["10.1016/j.toxlet.2022.08.006"],"eki":["1822645956"]},"name":{"displayForm":["Tim Brecklinghaus, Wiebke Albrecht, Julia Duda, Franziska Kappenberg, Lisa Gründler, Karolina Edlund, Rosemarie Marchan, Ahmed Ghallab, Cristina Cadenas, Adrian Rieck, Nachiket Vartak, Laia Tolosa, José V. Castell, Iain Gardner, Emina Halilbasic, Michael Trauner, Anett Ullrich, Anja Zeigerer, Özlem Demirci Turgunbayer, Georg Damm, Daniel Seehofer, Jörg Rahnenführer, Jan G. Hengstler"]}} | ||
| SRT | |a BRECKLINGHINVITROINS1202 | ||