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The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice

Clinicians often hesitate prescribing corticosteroids to treat corticosteroid-responsive conditions in sickle cell disease (SCD) patients because their use can be associated with complications (increased hospital readmission, rebound pain, strokes, avascular necrosis, acute chest syndrome). Conseque...

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Autores principales: Almeida, Luis E. F., Damsker, Jesse M., Albani, Sarah, Afsar, Nina, Kamimura, Sayuri, Pratt, Drew, Kleiner, David E., Quezado, Martha, Gordish-Dressman, Heather, Quezado, Zenaide M. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904156/
https://www.ncbi.nlm.nih.gov/pubmed/29666400
http://dx.doi.org/10.1038/s41598-018-24274-6
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author Almeida, Luis E. F.
Damsker, Jesse M.
Albani, Sarah
Afsar, Nina
Kamimura, Sayuri
Pratt, Drew
Kleiner, David E.
Quezado, Martha
Gordish-Dressman, Heather
Quezado, Zenaide M. N.
author_facet Almeida, Luis E. F.
Damsker, Jesse M.
Albani, Sarah
Afsar, Nina
Kamimura, Sayuri
Pratt, Drew
Kleiner, David E.
Quezado, Martha
Gordish-Dressman, Heather
Quezado, Zenaide M. N.
author_sort Almeida, Luis E. F.
collection PubMed
description Clinicians often hesitate prescribing corticosteroids to treat corticosteroid-responsive conditions in sickle cell disease (SCD) patients because their use can be associated with complications (increased hospital readmission, rebound pain, strokes, avascular necrosis, acute chest syndrome). Consequently, SCD patients may receive suboptimal treatment for corticosteroid-responsive conditions. We conducted a preclinical trial of dissociative (vamorolone) and conventional (prednisolone) corticosteroid compounds to evaluate their effects on nociception phenotype, inflammation, and organ dysfunction in SCD mice. Prednisolone and vamorolone had no significant effects on nociception phenotype or anemia in homozygous mice. Conversely, prednisolone and vamorolone significantly decreased white blood cell counts and hepatic inflammation. Interestingly, the effects of vamorolone were milder than those of prednisolone, as vamorolone yielded less attenuation of hepatic inflammation compared to prednisolone. Compared to controls and heterozygotes, homozygotes had significant liver necrosis, which was significantly exacerbated by prednisolone and vamorolone despite decreased hepatic inflammation. These hepatic histopathologic changes were associated with increases in transaminases and alkaline phosphatase. Together, these results suggest that, even in the setting of decreasing hepatic inflammation, prednisolone and vamorolone were associated with significant hepatic toxicity in SCD mice. These findings raise the possibility that hepatic function deterioration could occur with the use of corticosteroids (conventional and dissociative) in SCD.
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spelling pubmed-59041562018-04-25 The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice Almeida, Luis E. F. Damsker, Jesse M. Albani, Sarah Afsar, Nina Kamimura, Sayuri Pratt, Drew Kleiner, David E. Quezado, Martha Gordish-Dressman, Heather Quezado, Zenaide M. N. Sci Rep Article Clinicians often hesitate prescribing corticosteroids to treat corticosteroid-responsive conditions in sickle cell disease (SCD) patients because their use can be associated with complications (increased hospital readmission, rebound pain, strokes, avascular necrosis, acute chest syndrome). Consequently, SCD patients may receive suboptimal treatment for corticosteroid-responsive conditions. We conducted a preclinical trial of dissociative (vamorolone) and conventional (prednisolone) corticosteroid compounds to evaluate their effects on nociception phenotype, inflammation, and organ dysfunction in SCD mice. Prednisolone and vamorolone had no significant effects on nociception phenotype or anemia in homozygous mice. Conversely, prednisolone and vamorolone significantly decreased white blood cell counts and hepatic inflammation. Interestingly, the effects of vamorolone were milder than those of prednisolone, as vamorolone yielded less attenuation of hepatic inflammation compared to prednisolone. Compared to controls and heterozygotes, homozygotes had significant liver necrosis, which was significantly exacerbated by prednisolone and vamorolone despite decreased hepatic inflammation. These hepatic histopathologic changes were associated with increases in transaminases and alkaline phosphatase. Together, these results suggest that, even in the setting of decreasing hepatic inflammation, prednisolone and vamorolone were associated with significant hepatic toxicity in SCD mice. These findings raise the possibility that hepatic function deterioration could occur with the use of corticosteroids (conventional and dissociative) in SCD. Nature Publishing Group UK 2018-04-17 /pmc/articles/PMC5904156/ /pubmed/29666400 http://dx.doi.org/10.1038/s41598-018-24274-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Almeida, Luis E. F.
Damsker, Jesse M.
Albani, Sarah
Afsar, Nina
Kamimura, Sayuri
Pratt, Drew
Kleiner, David E.
Quezado, Martha
Gordish-Dressman, Heather
Quezado, Zenaide M. N.
The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title_full The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title_fullStr The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title_full_unstemmed The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title_short The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
title_sort corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904156/
https://www.ncbi.nlm.nih.gov/pubmed/29666400
http://dx.doi.org/10.1038/s41598-018-24274-6
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