3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis
APAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2022-03-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/13082.pdf |
| _version_ | 1827607512179802112 |
|---|---|
| author | Tianyu Liu Lei Yang Hejun Gao Yuzhen Zhuo Zhengwei Tu Yongqin Wang Jing Xun Qi Zhang Lanqiu Zhang Ximo Wang |
| author_facet | Tianyu Liu Lei Yang Hejun Gao Yuzhen Zhuo Zhengwei Tu Yongqin Wang Jing Xun Qi Zhang Lanqiu Zhang Ximo Wang |
| author_sort | Tianyu Liu |
| collection | DOAJ |
| description | APAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects. However, the effects of DAG on acute liver failure (ALF) are largely unknown. The purpose of this study is to study the protective effects and mechanism of DAG on APAP-induced ALF in mice. We established an ALF model in adult male pathogen-free C57BL/6 mice treated with APAP (300 mg/kg) by intraperitoneal injection and resolved by 24 h. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in mouse liver tissue. The infiltration of neutrophils in liver tissue and reactive oxygen species (ROS) in AML12 cells were analyzed by flow cytometry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were analyzed using relevant kits. Our results show that DAG reduced APAP-induced serum ALT and AST levels, histopathological changes, liver neutrophil infiltration and proinflammatory cytokines production, also attenuated the accumulation of MDA and the exhaustion of GSH, CAT and SOD. In vitro experiment indicated that DAG dose-dependently inhibited APAP-induced the levels of pro-inflammatory factors (IL-1β and IL18), and reactive oxygen species (ROS) and preventing GSH depletion in mouse AML12 hepatocytes. More interestingly, DAG inhibited the expression of ERK, HO-1, NLRP3, Caspase1 (p20) and Gasdermin-D and upregulated the expression of GPX4 in liver tissues and AML12hepatocytes. Therefore, our results indicate that DAG may act as a potential agent to treat ALF induced by APAP by inhibiting hepatocyte ferroptosis and pyroptosis. |
| first_indexed | 2024-03-09T06:55:16Z |
| format | Article |
| id | doaj.art-85bdd75ea6594e758683729ec7ee877b |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:55:16Z |
| publishDate | 2022-03-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-85bdd75ea6594e758683729ec7ee877b2023-12-03T10:04:17ZengPeerJ Inc.PeerJ2167-83592022-03-0110e1308210.7717/peerj.130823,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosisTianyu Liu0Lei Yang1Hejun Gao2Yuzhen Zhuo3Zhengwei Tu4Yongqin Wang5Jing Xun6Qi Zhang7Lanqiu Zhang8Ximo Wang9Tianjin Medical University, Tianjin, ChinaTianjin Nankai Hospital, Tianjin, ChinaTianjin Medical University, Tianjin, ChinaTianjin Nankai Hospital, Tianjin, ChinaTianjin Nankai Hospital, Tianjin, ChinaThe Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, ChinaTianjin Nankai Hospital, Tianjin, ChinaTianjin Nankai Hospital, Tianjin, ChinaTianjin Nankai Hospital, Tianjin, ChinaTianjin Medical University, Tianjin, ChinaAPAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects. However, the effects of DAG on acute liver failure (ALF) are largely unknown. The purpose of this study is to study the protective effects and mechanism of DAG on APAP-induced ALF in mice. We established an ALF model in adult male pathogen-free C57BL/6 mice treated with APAP (300 mg/kg) by intraperitoneal injection and resolved by 24 h. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in mouse liver tissue. The infiltration of neutrophils in liver tissue and reactive oxygen species (ROS) in AML12 cells were analyzed by flow cytometry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were analyzed using relevant kits. Our results show that DAG reduced APAP-induced serum ALT and AST levels, histopathological changes, liver neutrophil infiltration and proinflammatory cytokines production, also attenuated the accumulation of MDA and the exhaustion of GSH, CAT and SOD. In vitro experiment indicated that DAG dose-dependently inhibited APAP-induced the levels of pro-inflammatory factors (IL-1β and IL18), and reactive oxygen species (ROS) and preventing GSH depletion in mouse AML12 hepatocytes. More interestingly, DAG inhibited the expression of ERK, HO-1, NLRP3, Caspase1 (p20) and Gasdermin-D and upregulated the expression of GPX4 in liver tissues and AML12hepatocytes. Therefore, our results indicate that DAG may act as a potential agent to treat ALF induced by APAP by inhibiting hepatocyte ferroptosis and pyroptosis.https://peerj.com/articles/13082.pdfAcetaminophenAcute liver failureFerroptosisPyroptosis3,4-dihydroxyphenylethyl alcohol glycoside |
| spellingShingle | Tianyu Liu Lei Yang Hejun Gao Yuzhen Zhuo Zhengwei Tu Yongqin Wang Jing Xun Qi Zhang Lanqiu Zhang Ximo Wang 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis PeerJ Acetaminophen Acute liver failure Ferroptosis Pyroptosis 3,4-dihydroxyphenylethyl alcohol glycoside |
| title | 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| title_full | 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| title_fullStr | 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| title_full_unstemmed | 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| title_short | 3,4-dihydroxyphenylethyl alcohol glycoside reduces acetaminophen-induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| title_sort | 3 4 dihydroxyphenylethyl alcohol glycoside reduces acetaminophen induced acute liver failure in mice by inhibiting hepatocyte ferroptosis and pyroptosis |
| topic | Acetaminophen Acute liver failure Ferroptosis Pyroptosis 3,4-dihydroxyphenylethyl alcohol glycoside |
| url | https://peerj.com/articles/13082.pdf |
| work_keys_str_mv | AT tianyuliu 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT leiyang 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT hejungao 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT yuzhenzhuo 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT zhengweitu 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT yongqinwang 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT jingxun 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT qizhang 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT lanqiuzhang 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis AT ximowang 34dihydroxyphenylethylalcoholglycosidereducesacetaminopheninducedacuteliverfailureinmicebyinhibitinghepatocyteferroptosisandpyroptosis |