Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation
Background Hepatic ischemia-reperfusion injury (IRI) is a common innate immune-mediated sterile inflammatory response in liver transplantation and liver tumor resection. Neutrophil extracellular traps (NETs) can aggravate liver injury and activates innate immune response in the process of liver IRI....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Investigative Surgery |
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| Online Access: | http://dx.doi.org/10.1080/08941939.2022.2164813 |
| _version_ | 1797684458707484672 |
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| author | Cunle Zhu Shangheng Shi Peng Jiang Xijian Huang Jinxin Zhao Yan Jin Yuntai Shen Xin Zhou Huan Liu Jinzhen Cai |
| author_facet | Cunle Zhu Shangheng Shi Peng Jiang Xijian Huang Jinxin Zhao Yan Jin Yuntai Shen Xin Zhou Huan Liu Jinzhen Cai |
| author_sort | Cunle Zhu |
| collection | DOAJ |
| description | Background Hepatic ischemia-reperfusion injury (IRI) is a common innate immune-mediated sterile inflammatory response in liver transplantation and liver tumor resection. Neutrophil extracellular traps (NETs) can aggravate liver injury and activates innate immune response in the process of liver IRI. However, Curcumin (Cur) can reverse this damage and reduce NETs formation. Nevertheless, the specific regulatory mechanism is still unclear in liver IRI. This study aimed to explore the potential mechanisms that how does Cur alleviate hepatic IRI by inhibits NETs production and develop novel treatment regimens. Methods We established a hepatic IRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 2 h, 6 h, 12 h, and 24 h respectively. Subsequently, we were separated into 5 groups, namely the I/R group, Cur group, DNase-1 group, Cur + DNase1 group and sham operation group. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Hematoxylin-eosin staining, immunofluorescence, and TUNEL analysis were applied to assess liver injury degree and NETs levels. Western blot assay was used to detect the protein levels of apoptosis-related proteins and MEK pathway proteins. Results Cur could alleviate hepatic IRI by inhibiting the generation of NETs via suppressing the MEK/ERK pathway. In addition, this study also revealed that DNase-1 is vital for alleviating hepatic IRI by reducing the generation of NETs. Conclusions Cur combined with DNase-1 was more effective than the two drugs administered alone in alleviating hepatic IRI by inhibiting the generation of NETs. These results also suggested that curcumin combined with DNase-1 was a potential therapeutic strategy to mitigate hepatic IRI. |
| first_indexed | 2024-03-12T00:29:56Z |
| format | Article |
| id | doaj.art-3c5719b3e8d942509ee77afa01312ac6 |
| institution | Directory Open Access Journal |
| issn | 0894-1939 1521-0553 |
| language | English |
| last_indexed | 2024-03-12T00:29:56Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Investigative Surgery |
| spelling | doaj.art-3c5719b3e8d942509ee77afa01312ac62023-09-15T10:21:30ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532023-12-0136110.1080/08941939.2022.21648132164813Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps FormationCunle Zhu0Shangheng Shi1Peng Jiang2Xijian Huang3Jinxin Zhao4Yan Jin5Yuntai Shen6Xin Zhou7Huan Liu8Jinzhen Cai9The Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityThe Institute of Transplantation Science, Qingdao UniversityOrgan Transplantation Center, The Institute of Transplantation Science, The Affiliated Hospital of Qingdao UniversityOrgan Transplantation Center, The Institute of Transplantation Science, The Affiliated Hospital of Qingdao UniversityBackground Hepatic ischemia-reperfusion injury (IRI) is a common innate immune-mediated sterile inflammatory response in liver transplantation and liver tumor resection. Neutrophil extracellular traps (NETs) can aggravate liver injury and activates innate immune response in the process of liver IRI. However, Curcumin (Cur) can reverse this damage and reduce NETs formation. Nevertheless, the specific regulatory mechanism is still unclear in liver IRI. This study aimed to explore the potential mechanisms that how does Cur alleviate hepatic IRI by inhibits NETs production and develop novel treatment regimens. Methods We established a hepatic IRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 2 h, 6 h, 12 h, and 24 h respectively. Subsequently, we were separated into 5 groups, namely the I/R group, Cur group, DNase-1 group, Cur + DNase1 group and sham operation group. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Hematoxylin-eosin staining, immunofluorescence, and TUNEL analysis were applied to assess liver injury degree and NETs levels. Western blot assay was used to detect the protein levels of apoptosis-related proteins and MEK pathway proteins. Results Cur could alleviate hepatic IRI by inhibiting the generation of NETs via suppressing the MEK/ERK pathway. In addition, this study also revealed that DNase-1 is vital for alleviating hepatic IRI by reducing the generation of NETs. Conclusions Cur combined with DNase-1 was more effective than the two drugs administered alone in alleviating hepatic IRI by inhibiting the generation of NETs. These results also suggested that curcumin combined with DNase-1 was a potential therapeutic strategy to mitigate hepatic IRI.http://dx.doi.org/10.1080/08941939.2022.2164813neutrophil extracellular traps (nets)hepatic ischemia reperfusion injurycurcumin (cur)dnase-1 |
| spellingShingle | Cunle Zhu Shangheng Shi Peng Jiang Xijian Huang Jinxin Zhao Yan Jin Yuntai Shen Xin Zhou Huan Liu Jinzhen Cai Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation Journal of Investigative Surgery neutrophil extracellular traps (nets) hepatic ischemia reperfusion injury curcumin (cur) dnase-1 |
| title | Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation |
| title_full | Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation |
| title_fullStr | Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation |
| title_full_unstemmed | Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation |
| title_short | Curcumin Alleviates Hepatic Ischemia-Reperfusion Injury by Inhibiting Neutrophil Extracellular Traps Formation |
| title_sort | curcumin alleviates hepatic ischemia reperfusion injury by inhibiting neutrophil extracellular traps formation |
| topic | neutrophil extracellular traps (nets) hepatic ischemia reperfusion injury curcumin (cur) dnase-1 |
| url | http://dx.doi.org/10.1080/08941939.2022.2164813 |
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