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Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver

Dimethyl sulfoxide (DMSO) is widely used as a solvent for small hydrophobic drug molecules. However, the safe volume allowing to avoid its embryotoxic effect has been poorly studied. In this study, we documented the effects of dimethyl sulfoxide (DMSO) in the developing chicken embryo at morphologic...

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Autores principales: Luptakova, Lenka, Dvorcakova, Simona, Demcisakova, Zuzana, Belbahri, Lassaad, Holovska, Katarina, Petrovova, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001493/
https://www.ncbi.nlm.nih.gov/pubmed/33809222
http://dx.doi.org/10.3390/toxics9030055
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author Luptakova, Lenka
Dvorcakova, Simona
Demcisakova, Zuzana
Belbahri, Lassaad
Holovska, Katarina
Petrovova, Eva
author_facet Luptakova, Lenka
Dvorcakova, Simona
Demcisakova, Zuzana
Belbahri, Lassaad
Holovska, Katarina
Petrovova, Eva
author_sort Luptakova, Lenka
collection PubMed
description Dimethyl sulfoxide (DMSO) is widely used as a solvent for small hydrophobic drug molecules. However, the safe volume allowing to avoid its embryotoxic effect has been poorly studied. In this study, we documented the effects of dimethyl sulfoxide (DMSO) in the developing chicken embryo at morphological, histological, and molecular levels. We focused on the developing chicken liver as the main organ involved in the process of detoxification. In our study, 100% DMSO was administered subgerminally onto the eggshell membrane (membrana papyracea) at various volumes (5, 10, 15, 20, 25, 30, 35, and 50 µL) on 4th embryonic day (ED). We focused on histopathological alterations of the liver structure, and noticed the overall impact of DMSO on developing chicken embryos (embryotoxicity, malformation). At the molecular level, we studied cytochrome P450 complex (CYP) isoform’s activities in relation to changes of CYP1A5, CYP3A37, and CYP3A80 gene expression. Total embryotoxicity after application of different doses of DMSO on ED 4, and the embryo lethality increased with increasing DMSO amounts. Overall mortality after DMSO administration ranged below 33%. Mortality was increased with higher amounts of DMSO, mainly from 20 µL. The highest mortality was observed for the highest dose of DMSO over 35 µL. The results also showed a decrease in body weight with increased application volumes of DMSO. At the histological level, we observed mainly the presence of lipid droplets and dilated bile canaliculi and sinusoids in samples over the administration of 25 µL of DMSO. While these findings were not statistically significant, DMSO treatment caused a significant different up-regulation of mRNA expression in all studied genes. For CYP1A5, CYP3A37, and CYP3A80 DMSO volumes needed were 15 µL, 10 µL, and 20 µL, respectively. A significant down-regulation of all studied CYP isoform was detected after application of a DMSO dose of 5 µL. Regarding the morphological results, we can assume that the highest safe dose of DMSO without affecting chicken embryo development and its liver is up to 10 µL. This conclusion is corroborated with the presence of number of malformations and body weight reduction, which correlates with histological findings. Moreover, the gene expression results showed that even the lowest administered DMSO volume could affect hepatocytes at the molecular level causing down-regulation of cytochrome P450 complex (CYP1A5, CYP3A37, CYP3A80).
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spelling pubmed-80014932021-03-28 Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver Luptakova, Lenka Dvorcakova, Simona Demcisakova, Zuzana Belbahri, Lassaad Holovska, Katarina Petrovova, Eva Toxics Article Dimethyl sulfoxide (DMSO) is widely used as a solvent for small hydrophobic drug molecules. However, the safe volume allowing to avoid its embryotoxic effect has been poorly studied. In this study, we documented the effects of dimethyl sulfoxide (DMSO) in the developing chicken embryo at morphological, histological, and molecular levels. We focused on the developing chicken liver as the main organ involved in the process of detoxification. In our study, 100% DMSO was administered subgerminally onto the eggshell membrane (membrana papyracea) at various volumes (5, 10, 15, 20, 25, 30, 35, and 50 µL) on 4th embryonic day (ED). We focused on histopathological alterations of the liver structure, and noticed the overall impact of DMSO on developing chicken embryos (embryotoxicity, malformation). At the molecular level, we studied cytochrome P450 complex (CYP) isoform’s activities in relation to changes of CYP1A5, CYP3A37, and CYP3A80 gene expression. Total embryotoxicity after application of different doses of DMSO on ED 4, and the embryo lethality increased with increasing DMSO amounts. Overall mortality after DMSO administration ranged below 33%. Mortality was increased with higher amounts of DMSO, mainly from 20 µL. The highest mortality was observed for the highest dose of DMSO over 35 µL. The results also showed a decrease in body weight with increased application volumes of DMSO. At the histological level, we observed mainly the presence of lipid droplets and dilated bile canaliculi and sinusoids in samples over the administration of 25 µL of DMSO. While these findings were not statistically significant, DMSO treatment caused a significant different up-regulation of mRNA expression in all studied genes. For CYP1A5, CYP3A37, and CYP3A80 DMSO volumes needed were 15 µL, 10 µL, and 20 µL, respectively. A significant down-regulation of all studied CYP isoform was detected after application of a DMSO dose of 5 µL. Regarding the morphological results, we can assume that the highest safe dose of DMSO without affecting chicken embryo development and its liver is up to 10 µL. This conclusion is corroborated with the presence of number of malformations and body weight reduction, which correlates with histological findings. Moreover, the gene expression results showed that even the lowest administered DMSO volume could affect hepatocytes at the molecular level causing down-regulation of cytochrome P450 complex (CYP1A5, CYP3A37, CYP3A80). MDPI 2021-03-12 /pmc/articles/PMC8001493/ /pubmed/33809222 http://dx.doi.org/10.3390/toxics9030055 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Luptakova, Lenka
Dvorcakova, Simona
Demcisakova, Zuzana
Belbahri, Lassaad
Holovska, Katarina
Petrovova, Eva
Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title_full Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title_fullStr Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title_full_unstemmed Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title_short Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver
title_sort dimethyl sulfoxide: morphological, histological, and molecular view on developing chicken liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001493/
https://www.ncbi.nlm.nih.gov/pubmed/33809222
http://dx.doi.org/10.3390/toxics9030055
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