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 (<i>Panax ginseng</i>, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen...
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MDPI AG
2019-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/8/9/395 |
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| author | Zi Wang Weinan Hao Junnan Hu Xiaojie Mi Ye Han Shen Ren Shuang Jiang Yingping Wang Xindian Li Wei Li |
| author_facet | Zi Wang Weinan Hao Junnan Hu Xiaojie Mi Ye Han Shen Ren Shuang Jiang Yingping Wang Xindian Li Wei Li |
| author_sort | Zi Wang |
| collection | DOAJ |
| description | Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (<i>Panax ginseng</i>, 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. |
| first_indexed | 2024-03-12T07:52:51Z |
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| id | doaj.art-65c116d4f67e43cf9f4955beb2e677f9 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T07:52:51Z |
| publishDate | 2019-09-01 |
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| series | Antioxidants |
| spelling | doaj.art-65c116d4f67e43cf9f4955beb2e677f92023-09-02T20:29:56ZengMDPI AGAntioxidants2076-39212019-09-018939510.3390/antiox8090395antiox8090395Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal PathwaysZi Wang0Weinan Hao1Junnan Hu2Xiaojie Mi3Ye Han4Shen Ren5Shuang Jiang6Yingping Wang7Xindian Li8Wei Li9College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaMaltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (<i>Panax ginseng</i>, 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.https://www.mdpi.com/2076-3921/8/9/395maltolacetaminophenliver injuryoxidative stressapoptosisinflammation response |
| spellingShingle | Zi Wang Weinan Hao Junnan Hu Xiaojie Mi Ye Han Shen Ren Shuang Jiang Yingping Wang Xindian Li Wei Li Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways Antioxidants maltol acetaminophen liver injury oxidative stress apoptosis inflammation response |
| 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 | maltol acetaminophen liver injury oxidative stress apoptosis inflammation response |
| url | https://www.mdpi.com/2076-3921/8/9/395 |
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