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Wu W, Xu B, Huang H, Mao Y, Gao Y, Bu W. The role of ferroptosis in liver injury after cold ischemia-reperfusion in rats with autologous orthotopic liver transplantation. J Artif Organs 2025:10.1007/s10047-024-01488-2. [PMID: 39760970 DOI: 10.1007/s10047-024-01488-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025]
Abstract
Using autologous orthotopic liver transplantation (AOLT) model in rats, the effect of lipid reactive oxygen species (L-ROS) inhibitor Ferrostain-1 on ferroptosis signal pathway was observed to determine whether ferroptosis occurred in rat liver injury after cold ischemia-reperfusion (I/R). Thirty-two healthy adult SPF male SD rats, 8 ~ 10 weeks old, weight 240 ~ 260 g, were divided into four groups by the method of random number table (n = 8): sham group, I/R group, I/R + Fer-1 group, I/R + DFO group. In the I/R + Fer-1 group, ferristatin-1(5 mg /kg) was intraperitoneally injected 30 min before surgery; in the I/R + DFO group, DFO 100 mg/kg was injected intraperitoneally 1 h before operation and 12 h after operation. Blood samples were taken from the inferior hepatic vena cava 24 h after reperfusion. After anesthesia, the rats were killed and part of their liver tissue was removed. The pathological changes of liver tissue sections were observed under a high-power microscope, and the liver injury was evaluated. Serum malondialdehyde (MDA) and serum levels of ALT, AST and IL-6 were determined by the ELISA method, Reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), MDA, Fe2 + and superoxide dismutase (SOD) were determined in the liver tissue. Compared with the sham group, the serum levels of the IL-6,MDA, AST and ALT in I/R group were obviously higher (P < 0.05); The levels of MDA and Fe2+ in liver tissue were significantly increased (P < 0.05).The levels of SOD, GSH and GPX4 in liver tissue were decreased. The levels of serum MDA, IL-6, AST, and ALT in the I/R + Fer-1 and I/R + DFO groups were significantly lower than those in the I/R group at 24 h after reperfusion. In the I/R + Fer-1 group, the level of MDA in liver tissue decreased significantly, while the level of SOD, GSH and GPX4 in intestinal tissue increased (P < 0.05). In The I/R + DFO group, the levels of MDA and Fe2+ in liver tissue decreased significantly, while the level of SOD in intestinal tissue increased (P < 0.05). Ferroptosis is involved in pathophysiological process of liver injury after cold ischemia-reperfusion in AOLT rats.
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Affiliation(s)
- Wei Wu
- Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China.
| | - Bei Xu
- Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China
| | - Haibin Huang
- Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China
| | - Ying Mao
- Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China
| | - Yuan Gao
- Department of Anesthesiology, CR & WISCO General Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, 430080, China
| | - Wenhao Bu
- Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China.
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Shao JL, Wang LJ, Xiao J, Yang JF. Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury. World J Gastroenterol 2023; 29:4927-4941. [PMID: 37731999 PMCID: PMC10507504 DOI: 10.3748/wjg.v29.i33.4927] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 07/22/2023] [Accepted: 08/18/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.
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Affiliation(s)
- Jia-Li Shao
- Department of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Li-Juan Wang
- Department of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Ji Xiao
- Department of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Jin-Feng Yang
- Department of Anesthesiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
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Xie M, Xie R, Huang P, Yap DYH, Wu P. GADD45A and GADD45B as Novel Biomarkers Associated with Chromatin Regulators in Renal Ischemia-Reperfusion Injury. Int J Mol Sci 2023; 24:11304. [PMID: 37511062 PMCID: PMC10379085 DOI: 10.3390/ijms241411304] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/21/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023] Open
Abstract
Chromatin regulators (CRs) are essential upstream regulatory factors of epigenetic modification. The role of CRs in the pathogenesis of renal ischemia-reperfusion injury (IRI) remains unclear. We analyzed a bioinformatic analysis on the differentially expressed chromatin regulator genes in renal IRI patients using data from public domains. The hub CRs identified were used to develop a risk prediction model for renal IRI, and their expressions were also validated using Western blot, qRT-PCR, and immunohistochemistry in a murine renal IRI model. We also examined the relationships between hub CRs and infiltrating immune cells in renal IRI and used network analysis to explore drugs that target hub CRs and their relevant downstream microRNAs. The results of machine learning methods showed that five genes (DUSP1, GADD45A, GADD45B, GADD45G, HSPA1A) were upregulated in renal IRI, with key roles in the cell cycle, p38 MAPK signaling pathway, p53 signaling pathway, FoxO signaling pathway, and NF-κB signaling pathway. Two genes from the network, GADD45A and GADD45B (growth arrest and DNA damage-inducible protein 45 alpha and beta), were chosen for the renal IRI risk prediction model. They all showed good performance in the testing and validation cohorts. Mice with renal IRI showed significantly upregulated GADD45A and GADD45B expression within kidneys compared to sham-operated mice. GADD45A and GADD45B showed correlations with plasmacytoid dendritic cells (pDCs) in infiltrating immune cell analysis and enrichment in the MAPK pathway based on the weighted gene co-expression network analysis (WGCNA) method. Candidate drugs that target GADD45A and GADD45B include beta-escin, sertraline, primaquine, pimozide, and azacyclonol. The dysregulation of GADD45A and GADD45B is related to renal IRI and the infiltration of pDCs, and drugs that target GADD45A and GADD45B may have therapeutic potential for renal IRI.
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Affiliation(s)
- Ming Xie
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Ruiyan Xie
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong 999077, China
| | - Pengcheng Huang
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Desmond Y H Yap
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong 999077, China
| | - Peng Wu
- Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Wang L, Shao J, Su C, Yang J. The application of optical technology in the diagnosis and therapy of oxidative stress-mediated hepatic ischemia-reperfusion injury. Front Bioeng Biotechnol 2023; 11:1133039. [PMID: 36890921 PMCID: PMC9986550 DOI: 10.3389/fbioe.2023.1133039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/09/2023] [Indexed: 02/22/2023] Open
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is defined as liver tissue damage and cell death caused by reperfusion during liver transplantation or hepatectomy. Oxidative stress is one of the important mechanisms of HIRI. Studies have shown that the incidence of HIRI is very high, however, the number of patients who can get timely and efficient treatment is small. The reason is not hard to explain that invasive ways of detection and lack of timely of diagnostic methods. Hence, a new detection method is urgently needed in clinic application. Reactive oxygen species (ROS), which are markers of oxidative stress in the liver, could be detected by optical imaging and offer timely and effective non-invasive diagnosis and monitoring. Optical imaging could become the most potential tool of diagnosis of HIRI in the future. In addition, optical technology can also be used in disease treatment. It found that optical therapy has the function of anti-oxidative stress. Consequently, it has possibility to treat HIRI caused by oxidative stress. In this review, we mainly summarized the application and prospect of optical techniques in oxidative stress-induced by HIRI.
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Affiliation(s)
- Lijuan Wang
- Department of Medicine, Hengyang Medical School, University of South China, Hengyang, China.,Department of Anesthesiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jiali Shao
- Department of Anesthesiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Chen Su
- Department of Anesthesiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jinfeng Yang
- Department of Anesthesiology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
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