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Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis
INTRODUCTION: The effects of isoform-specific histone deacetylase inhibitors (HDACIs) and the non-selective HDACI on sepsis have been profoundly reported. However, the best HDAC classes have not been fully evaluated. Therefore, this study aimed to determine which HDACIs are responsible for survival...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015250/ https://www.ncbi.nlm.nih.gov/pubmed/36936452 http://dx.doi.org/10.1016/j.sopen.2023.03.003 |
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author | Niu, Kunwei Qu, Shibin Yang, Long Zhang, Hong Yuan, Juzheng Fan, Hanlu Li, Xiao Tao, Kaishan |
author_facet | Niu, Kunwei Qu, Shibin Yang, Long Zhang, Hong Yuan, Juzheng Fan, Hanlu Li, Xiao Tao, Kaishan |
author_sort | Niu, Kunwei |
collection | PubMed |
description | INTRODUCTION: The effects of isoform-specific histone deacetylase inhibitors (HDACIs) and the non-selective HDACI on sepsis have been profoundly reported. However, the best HDAC classes have not been fully evaluated. Therefore, this study aimed to determine which HDACIs are responsible for survival and beneficial for organ injury. METHODS: Experiment I, SD rats were subjected to cecal ligation and puncture and randomly assigned to the no treatment, dimethyl sulfoxide (DMSO) only, MS-275, LMK-235, tubastatinA (TubA), trichostatin-A (TSA), and sirtinol groups (n = 5). Survival was monitored for 48 h. Experiment II, the animals were monitored for 12 h, then, blood and tissues sample were collected. Interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) expressions were evaluated using ELISA. Liver, heart and lung tissues were analysed via hematoxylin and eosin staining. Liver and heart tissue lysates were analysed for acetylated histones H3, H4, a-tubulin and nuclear factor kappa B (NF-κB), IL-6, IL-1β, and TNF-α using western blotting. Splenocytes were examined via flow cytometry to analyse the immune cell population. RESULTS: MS-275, TubA and TSA treatments significantly prolonged survival. MS-275, LMK-235, TubA and TSA significantly reduced the histopathological scores and AST, ALT, CK, LDH, IL-6, IL-1β and TNF-α levels, significantly increased acetylated of NF-κB and changed the immune cell proportion. CONCLUSION: Our results indicated that HDACI classes I and IIb and non-selective HDACI can significantly prolong survival. Moreover, non-selective and isoform-specific class I and IIa/IIb HDACIs can attenuate inflammation and organ injury. |
format | Online Article Text |
id | pubmed-10015250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100152502023-03-16 Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis Niu, Kunwei Qu, Shibin Yang, Long Zhang, Hong Yuan, Juzheng Fan, Hanlu Li, Xiao Tao, Kaishan Surg Open Sci Research Paper INTRODUCTION: The effects of isoform-specific histone deacetylase inhibitors (HDACIs) and the non-selective HDACI on sepsis have been profoundly reported. However, the best HDAC classes have not been fully evaluated. Therefore, this study aimed to determine which HDACIs are responsible for survival and beneficial for organ injury. METHODS: Experiment I, SD rats were subjected to cecal ligation and puncture and randomly assigned to the no treatment, dimethyl sulfoxide (DMSO) only, MS-275, LMK-235, tubastatinA (TubA), trichostatin-A (TSA), and sirtinol groups (n = 5). Survival was monitored for 48 h. Experiment II, the animals were monitored for 12 h, then, blood and tissues sample were collected. Interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) expressions were evaluated using ELISA. Liver, heart and lung tissues were analysed via hematoxylin and eosin staining. Liver and heart tissue lysates were analysed for acetylated histones H3, H4, a-tubulin and nuclear factor kappa B (NF-κB), IL-6, IL-1β, and TNF-α using western blotting. Splenocytes were examined via flow cytometry to analyse the immune cell population. RESULTS: MS-275, TubA and TSA treatments significantly prolonged survival. MS-275, LMK-235, TubA and TSA significantly reduced the histopathological scores and AST, ALT, CK, LDH, IL-6, IL-1β and TNF-α levels, significantly increased acetylated of NF-κB and changed the immune cell proportion. CONCLUSION: Our results indicated that HDACI classes I and IIb and non-selective HDACI can significantly prolong survival. Moreover, non-selective and isoform-specific class I and IIa/IIb HDACIs can attenuate inflammation and organ injury. Elsevier 2023-03-02 /pmc/articles/PMC10015250/ /pubmed/36936452 http://dx.doi.org/10.1016/j.sopen.2023.03.003 Text en © 2023 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Niu, Kunwei Qu, Shibin Yang, Long Zhang, Hong Yuan, Juzheng Fan, Hanlu Li, Xiao Tao, Kaishan Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title | Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title_full | Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title_fullStr | Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title_full_unstemmed | Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title_short | Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis |
title_sort | protective effect of hdacis in improves survival and organ injury after clp-induced sepsis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015250/ https://www.ncbi.nlm.nih.gov/pubmed/36936452 http://dx.doi.org/10.1016/j.sopen.2023.03.003 |
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