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Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

BACKGROUND: Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19). APAP misuse would lead to liver injury. Diacerein (DIA), an anthraquinone derivative, has antioxidant and inflammatory...

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Autores principales: Mohamed Kamel, Gellan Alaa, Harahsheh, Eman, Hussein, Shaimaa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975726/
https://www.ncbi.nlm.nih.gov/pubmed/35366176
http://dx.doi.org/10.1007/s11033-022-07366-5
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author Mohamed Kamel, Gellan Alaa
Harahsheh, Eman
Hussein, Shaimaa
author_facet Mohamed Kamel, Gellan Alaa
Harahsheh, Eman
Hussein, Shaimaa
author_sort Mohamed Kamel, Gellan Alaa
collection PubMed
description BACKGROUND: Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19). APAP misuse would lead to liver injury. Diacerein (DIA), an anthraquinone derivative, has antioxidant and inflammatory properties. Hence, this study attempted to evaluate the impact of DIA treatment on liver injury induced by APAP and its influence on nuclear factor-κB (NF-κB) /toll-like receptor 4 (TLR4)/high mobility group box-1(HMGB-1) signaling as well as the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression. METHODS: Male albino rats received 25 as well as 50 mg/kg/day DIA orally for seven days. One hour after the last administration, rats received APAP (1gm/kg, orally). For histopathological analysis, liver tissues and blood were collected, immunohistochemical (IHC) assay, biochemical assay, as well as quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: DIA markedly reduced liver injury markers and ameliorated histopathological changes. Moreover, DIA dose-dependently alleviated oxidative stress status caused by APAP administration along with inflammatory markers, including the level of interleukin-1 beta (IL-1β), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Furthermore, DIA downregulated protein levels as well as mRNA of HMGB-1, TLR4, NF-κB p65 expression, and enhanced PPAR-γ expression. Moreover, DIA ameliorated apoptotic (Bax) and caspase-3 expressions and increased the anti-apoptotic (Bcl2) expression. CONCLUSIONS: This study demonstrated that DIA exerts anti-apoptotic, anti-inflammatory, and antioxidant properties against liver injury induced by APAP that is attributed to inhibition of the HMGB1/TLR4/NF-κB pathway, besides upregulation of the expression of PPAR-γ.
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spelling pubmed-89757262022-04-04 Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal Mohamed Kamel, Gellan Alaa Harahsheh, Eman Hussein, Shaimaa Mol Biol Rep Original Article BACKGROUND: Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19). APAP misuse would lead to liver injury. Diacerein (DIA), an anthraquinone derivative, has antioxidant and inflammatory properties. Hence, this study attempted to evaluate the impact of DIA treatment on liver injury induced by APAP and its influence on nuclear factor-κB (NF-κB) /toll-like receptor 4 (TLR4)/high mobility group box-1(HMGB-1) signaling as well as the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression. METHODS: Male albino rats received 25 as well as 50 mg/kg/day DIA orally for seven days. One hour after the last administration, rats received APAP (1gm/kg, orally). For histopathological analysis, liver tissues and blood were collected, immunohistochemical (IHC) assay, biochemical assay, as well as quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: DIA markedly reduced liver injury markers and ameliorated histopathological changes. Moreover, DIA dose-dependently alleviated oxidative stress status caused by APAP administration along with inflammatory markers, including the level of interleukin-1 beta (IL-1β), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Furthermore, DIA downregulated protein levels as well as mRNA of HMGB-1, TLR4, NF-κB p65 expression, and enhanced PPAR-γ expression. Moreover, DIA ameliorated apoptotic (Bax) and caspase-3 expressions and increased the anti-apoptotic (Bcl2) expression. CONCLUSIONS: This study demonstrated that DIA exerts anti-apoptotic, anti-inflammatory, and antioxidant properties against liver injury induced by APAP that is attributed to inhibition of the HMGB1/TLR4/NF-κB pathway, besides upregulation of the expression of PPAR-γ. Springer Netherlands 2022-04-02 2022 /pmc/articles/PMC8975726/ /pubmed/35366176 http://dx.doi.org/10.1007/s11033-022-07366-5 Text en © The Author(s), under exclusive licence to Springer Nature B.V. 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Mohamed Kamel, Gellan Alaa
Harahsheh, Eman
Hussein, Shaimaa
Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title_full Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title_fullStr Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title_full_unstemmed Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title_short Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal
title_sort diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting hmgb1/tlr4/nf-κb and upregulating ppar-γ signal
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975726/
https://www.ncbi.nlm.nih.gov/pubmed/35366176
http://dx.doi.org/10.1007/s11033-022-07366-5
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