ArticleTransplantation2006
Attenuation of acute rejection in a rat liver transplantation model by a liver-targeted dextran prodrug of methylprednisolone.
Article in Transplantation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 18 citations in OpenAlex.
- Nanoparticle approaches for hepatitis therapy and clinical translation.Discover nano · 2026Review
- Using Tree Shrews (Tupaia belangeri) as a Novel Animal Model of Liver Transplantation.Current medical science · 2018Article
- Hepatic immunosuppressive effects of systemically administered novel dextran-methylprednisolone prodrugs with peptide linkers in rats.Journal of pharmaceutical sciences · 2012Article
- Plasma pharmacokinetics and tissue disposition of novel dextran-methylprednisolone conjugates with peptide linkers in rats.Journal of pharmaceutical sciences · 2010Article
- Liquid chromatography-tandem mass spectrometry for the determination of methylprednisolone in rat plasma and liver after intravenous administration of its liver-targeted dextran prodrug.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2009Article
- Synthesis and in vitro characterization of novel dextran-methylprednisolone conjugates with peptide linkers: effects of linker length on hydrolytic and enzymatic release of methylprednisolone and its peptidyl intermediates.Journal of pharmaceutical sciences · 2008Article
- Effects of methylprednisolone and its liver-targeted dextran prodrug on ischemia-reperfusion injury in a rat liver transplantation model.Pharmaceutical research · 2007Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe use of methylprednisolone (MP) and other corticosteroids for the treatment of acute liver allograft rejection is associated with severe toxicities in nontarget tissues. Therefore, selective delivery of MP to the liver may improve its efficacy and alleviate its side effects. We investigated the effects of a novel liver-targeted dextran prodrug of MP (DMP) in an orthotopic rat liver transplantation (OLT) model.
methodsThe model consisted of a high responder rejection strain combination (Dark Agouti donors and Lewis recipients). Liver recipients were intravenously administered saline or a single subtherapeutic dose of MP (5 mg/kg) as the parent drug (MP) or its prodrug (DMP). Different groups were then monitored for graft survival or euthanized 5 or 9 days posttransplantation. Plasma chemistry, including alkaline phosphatase and bilirubin, allograft histology, and survival duration were determined.
resultsUntreated recipients exhibited elevated plasma levels of liver injury markers, progressive portal and venous inflammation and cellular infiltration in liver allografts, and a mean graft survival time (MST) of 10.5 days. MP treatment did not alter any of these parameters. In contrast, a single dose of DMP resulted in a decrease in plasma levels of liver injury markers, a decrease in histological grade of rejection on day 5, and a substantial increase in MST (27.5 days).
conclusionsThese results demonstrate attenuation of acute rejection following local (allograft) immunosuppression with a single subtherapeutic dose of MP delivered as a liver-targeted prodrug. Dextran prodrugs may be useful for selective delivery of immunosuppressants to the liver following liver transplantation.
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