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Inflammation

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01.06.2015

Trichostatin A Protects Against Experimental Acute-on-Chronic Liver Failure in Rats Through Regulating the Acetylation of Nuclear Factor-κB

verfasst von: Qian Zhang, Fan Yang, Xun Li, Lu-wen Wang, Xiao-gang Chu, Hong Zhang, Zuo-jiong Gong

Erschienen in: Inflammation | Ausgabe 3/2015

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Abstract

Histone deacetylase inhibitors (HDACi) were recently shown to suppress inflammatory responses in experimental models of autoimmune and inflammatory diseases. In this study, the protective effects of Trichostatin A (TSA), an HDACi, on experimental acute-on-chronic liver failure (ACLF) in rat were explored. An ACLF model was established in rats, and animals were randomly divided into control, model, and TSA-treated groups. The rats in TSA-treated group received TSA (2 mg/kg) at 2 h before induction of ACLF. Samples were obtained at 24 h after ACLF induction. We found that the rats in model group showed severe damage to liver tissue at 24 h after ACLF induction. TSA improved liver injury effectively. Serum tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-10, and IL-18 levels were significantly increased in model group compared with control group, but TSA reduced serum TNF-α, IFN-γ, IL-10, and IL-18 levels effectively compared with model group. In addition, TSA reduced the total HDAC activity, promoted the acetylation of histone, and decreased the expressions of class I HDAC in liver tissue. TSA also increased the acetylation levels and decreased phosphorylation levels in NF-κB p65. The median survival time of the rats was significantly prolonged in TSA-treated group. To conclude, TSA can inhibit the release of multiple inflammatory cytokines, prolong the survival time, and protect against ACLF in rats. The mechanisms were probably through enhancing the acetylation levels of non-histones rather than histone.

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Titel: Trichostatin A Protects Against Experimental Acute-on-Chronic Liver Failure in Rats Through Regulating the Acetylation of Nuclear Factor-κB
verfasst von: Qian Zhang
Fan Yang
Xun Li
Lu-wen Wang
Xiao-gang Chu
Hong Zhang
Zuo-jiong Gong
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 3/2015
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-014-0108-7

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Trichostatin A Protects Against Experimental Acute-on-Chronic Liver Failure in Rats Through Regulating the Acetylation of Nuclear Factor-κB

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