The DOI matches its Crossref record.
Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury
Open accessAbstract
We examined the effects of upregulation of heme oxygenase-1 (HO-1) in steatotic rat liver models of ex vivo cold ischemia/reperfusion (I/R) injury. In the model of ischemia/isolated perfusion, treatment of genetically obese Zucker rats with the HO-1 inducer cobalt protoporphyrin (CoPP) or with adenoviral HO-1 (Ad-HO-1) significantly improved portal venous blood flow, increased bile production, and decreased hepatocyte injury. Unlike in untreated rats or those pretreated with the HO-1 inhibitor zinc protoporphyrin (ZnPP), upregulation of HO-1 by Western blots correlated with amelioration of histologic features of I/R injury. Adjunctive infusion of ZnPP abrogated the beneficial effects of Ad-HO-1 gene transfer, documenting the direct involvement of HO-1 in protection against I/R injury. Following cold ischemia/isotransplantation, HO-1 overexpression extended animal survival from 40% in untreated controls to about 80% after CoPP or Ad-HO-1 therapy. This effect correlated with preserved hepatic architecture, improved liver function, and depressed infiltration by T cells and macrophages. Hence, CoPP- or gene therapy-induced HO-1 prevented I/R injury in steatotic rat livers. These findings provide the rationale for refined new treatments that should increase the supply of usable donor livers and ultimately improve the overall success of liver transplantation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
Brouard, S., Otterbein, L. E., Anrather, J., Tobiasch, E., Bach, F. H., Choi, A. M. K., & Soares, M. P. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1015 · Cited by 984
Ischemia–Reperfusion–induced Lung Injury
de Perrot, M., Liu, M., Waddell, T. K., & Keshavjee, S. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200207-670so · Cited by 962
Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications
Wu, L., & Wang, R. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.4.3 · Cited by 962
Heme oxygenase: colors of defense against cellular stress
Otterbein, L. E., & Choi, A. M. K. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.279.6.l1029 · Cited by 870
Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning
Jaeschke, H. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00342.2002 · Cited by 852
Metadata
- Authors
- Amersi, F., Buelow, R., Kato, H., Ke, B., Coito, A. J., Shen, X.-D., Zhao, D., Zaky, J., Melinek, J., Lassman, C. R., Kolls, J. K., Alam, J., Ritter, T., Volk, H.-D., Farmer, D. G., Ghobrial, R. M., Busuttil, R. W., & Kupiec-Weglinski, J. W.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-12-01
- Volume
- 104
- Issue
- 11
- Pages
- 1631-1639
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2050971607
- Cited by
- 474
- References
- 0
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. https://app.cochat.ai/papers/10.1172/jci7903
- The paper
- Amersi, F., Buelow, R., Kato, H., Ke, B., Coito, A. J., Shen, X.-D., Zhao, D., Zaky, J., Melinek, J., Lassman, C. R., Kolls, J. K., Alam, J., Ritter, T., Volk, H.-D., Farmer, D. G., Ghobrial, R. M., Busuttil, R. W., & Kupiec-Weglinski, J. W. (1999). Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. Journal of Clinical Investigation. https://doi.org/10.1172/jci7903
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
