ArticleWorld journal of gastroenterology2015
Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 49 citations in OpenAlex.
- Dynamic regulation and targeted intervention of neutrophils in hepatic ischemia‑reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Multi-Pathway Mechanisms of Engeletin in Ischemic Stroke: A Comprehensive Study Based on Network Pharmacology, Machine Learning, and Immune Infiltration Analysis.International journal of molecular sciences · 2025Article
- USP15 as a Potential Therapeutic Target in Cerebral Ischemia: Modulation of Ferroptosis and Cognitive Dysfunction via the Nrf2/GPX4 Axis in Mice.Neuromolecular medicine · 2024Article
- Iron metabolism in colorectal cancer.Frontiers in oncology · 2023Review
- Hypoxia-inducible factor-1alpha protects the liver against ischemia-reperfusion injury by regulating the A2B adenosine receptor.Bioengineered · 2021Article
- Potential Role of Soluble Toll-like Receptors 2 and 4 as Therapeutic Agents in Stroke and Brain Hemorrhage.International journal of molecular sciences · 2021Review
- Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB AxisBalkan medical journal · 2020Article
- A Computational Approach for Mapping Heme Biology in the Context of Hemolytic Disorders.Frontiers in bioengineering and biotechnology · 2020Article
- RP105 alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways.International journal of molecular medicine · 2018Article
- Protective effects of heme oxygenase-1-transduced bone marrow-derived mesenchymal stem cells on reduced‑size liver transplantation: Role of autophagy regulated by the ERK/mTOR signaling pathway.International journal of molecular medicine · 2017Article
- Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways.Molecules (Basel, Switzerland) · 2017Article
- Dexmedetomidine Protects Rat Liver against Ischemia-Reperfusion Injury Partly by the α2A-Adrenoceptor Subtype and the Mechanism Is Associated with the TLR4/NF-κB Pathway.International journal of molecular sciences · 2016Article
- Blocking heme oxygenase-1 by zinc protoporphyrin reduces tumor hypoxia-mediated VEGF release and inhibits tumor angiogenesis as a potential therapeutic agent against colorectal cancer.Journal of biomedical science · 2016Article
- Marked protection against acute renal and hepatic injury after nitrited myoglobin + tin protoporphyrin administration.Translational research : the journal of laboratory and clinical medicine · 2015Article
- Mitochondrial Dysfunction and Autophagy in Hepatic Ischemia/Reperfusion Injury.BioMed research international · 2015Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the efficacy and molecular mechanisms of induced heme oxygenase (HO)-1 in protecting liver from warm ischemia/reperfusion (I/R) injury.
methodsPartial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75 min, followed by 6 h of reperfusion. Rats were treated with saline, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP) at 24 h prior to the ischemia insult. Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion. Serum transaminases level, plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured. Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis. We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines. The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β (TRIF) and anti-myeloid differentiation factor 88 (MyD88), and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.
resultsHO-1 protected livers from I/R injury, as evidenced by diminished liver enzymes and well-preserved tissue architecture. In comparison with ZnPP livers 6 h after surgery, CoPP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes, plasma cells, neutrophils and macrophages. The Toll-like receptor (TLR)-4 and TANK binding kinase 1 protein levels of rats treated with CoPP significantly reduced in TRIF-immunoprecipitated complex, as compared with ZnPP treatment. In addition, pretreatment with CoPP reduced the expression levels of TLR2, TLR4, IL-1R-associated kinase (IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in MyD88-immunoprecipitated complex. The inflammatory cytokines and chemokines mRNA expression rapidly decreased in CoPP-pretreated liver, compared with the ZnPP-treated group. However, the expression of negative regulators Toll-interacting protein, suppressor of cytokine signaling-1, IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in CoPP treatment rats were markedly up-regulated as compared with ZnPP-treated rats.
conclusionHO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered MyD88- and TRIF-dependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.
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