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Updated: May 5, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention by plant polyphenols
Zhi Zhong1, Henry D Connor, Mattias Froh
1Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 27599, USA. zzhong@med.unc.edu
Background & Aims:
The mechanisms by which small-for-size liver grafts decrease survival remain unclear. This study investigated the role of free radicals in injury to small-for-size grafts.
Methods:
Rat liver explants were reduced in size ex vivo and transplanted into recipients of the same or greater body weight, resulting in a graft weight and standard liver weight of approximately 50% and 25%, respectively. A polyphenol extract from Camellia sinenesis (20 microg/mL) or an equivalent concentration of epicatechin was added to the storage solution and the lactated Ringer poststorage rinse solution.
Results:
Serum alanine aminotransferase release increased from approximately 60 U/L before implantation to 750, 1410, and 2520 U/L after full-size, half-size, and quarter-size transplantation, respectively. Total bilirubin increased slightly after transplantation of full-size and half-size grafts but increased 104-fold in quarter-size grafts. In quarter-size grafts, histological changes included necrosis, leukocyte infiltration, and eosinophilic inclusion body formation. Polyphenol treatment ameliorated these effects by > or =67%. Survival was 30% after transplantation of small-for-size grafts. After polyphenol treatment, survival increased to 70%. Free radicals in bile assessed by spin trapping and 4-hydroxynonenal adducts measured by immunohistochemistry were also greater in reduced-size grafts, an effect ameliorated by polyphenols. Epicatechin, a major polyphenol from Camellia sinenesis, also improved graft function and decreased enzyme release, histopathologic changes, and free radical formation.
Conclusions:
Increased formation of free radicals occurs after transplantation of reduced-size livers, which contributes to graft dysfunction and failure. Plant polyphenols decrease liver graft injury and increase survival of small-for-size liver grafts, most likely by scavenging free radicals.
Insights
Small-for-size liver grafts cause injury due to free radicals. Plant polyphenols, like epicatechin, protect these grafts by reducing oxidative stress and improving survival rates in liver transplantation.
Area of Science:
- Hepatology
- Transplantation immunology
- Oxidative stress research
Background:
- Mechanisms of small-for-size liver graft failure are not well understood.
- Free radical-induced injury is a suspected contributor to reduced graft survival.
Purpose of the Study:
- To investigate the role of free radicals in small-for-size liver graft injury.
- To evaluate the protective effects of plant polyphenols against this injury.
Main Methods:
- Ex vivo reduction of rat liver grafts and transplantation into recipients.
- Administration of Camellia sinenesis polyphenol extract or epicatechin.
- Assessment of liver injury markers, histology, survival rates, and free radical formation.
Main Results:
- Small-for-size grafts showed significantly increased liver enzyme release, bilirubin levels, and histological damage.
- Polyphenol treatment ameliorated injury markers and improved graft survival from 30% to 70%.
- Increased free radical formation was observed in small grafts, and polyphenols reduced this oxidative stress.
Conclusions:
- Increased free radical formation contributes significantly to small-for-size liver graft dysfunction and failure.
- Plant-derived polyphenols, particularly epicatechin, offer a protective effect against liver graft injury.
- Polyphenols enhance survival of small-for-size liver grafts, likely through free radical scavenging mechanisms.
