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Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways
Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hep...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769439/ https://www.ncbi.nlm.nih.gov/pubmed/31547366 http://dx.doi.org/10.3390/antiox8090395 |
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author | Wang, Zi Hao, Weinan Hu, Junnan Mi, Xiaojie Han, Ye Ren, Shen Jiang, Shuang Wang, Yingping Li, Xindian Li, Wei |
author_facet | Wang, Zi Hao, Weinan Hu, Junnan Mi, Xiaojie Han, Ye Ren, Shen Jiang, Shuang Wang, Yingping Li, Xindian Li, Wei |
author_sort | Wang, Zi |
collection | PubMed |
description | Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway. |
format | Online Article Text |
id | pubmed-6769439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67694392019-10-30 Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways Wang, Zi Hao, Weinan Hu, Junnan Mi, Xiaojie Han, Ye Ren, Shen Jiang, Shuang Wang, Yingping Li, Xindian Li, Wei Antioxidants (Basel) Article Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway. MDPI 2019-09-12 /pmc/articles/PMC6769439/ /pubmed/31547366 http://dx.doi.org/10.3390/antiox8090395 Text en © 2019 by the authors. 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/). |
spellingShingle | Article Wang, Zi Hao, Weinan Hu, Junnan Mi, Xiaojie Han, Ye Ren, Shen Jiang, Shuang Wang, Yingping Li, Xindian Li, Wei Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title | Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title_full | Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title_fullStr | Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title_full_unstemmed | Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title_short | Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways |
title_sort | maltol improves apap-induced hepatotoxicity by inhibiting oxidative stress and inflammation response via nf-κb and pi3k/akt signal pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769439/ https://www.ncbi.nlm.nih.gov/pubmed/31547366 http://dx.doi.org/10.3390/antiox8090395 |
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