Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention by plant polyphenols.
OBJECTIVE
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.
Zhong
Zhi
Z
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 27599, USA. zzhong@med.unc.edu
Connor
Henry D
HD
Froh
Mattias
M
Bunzendahl
Hartwig
H
Lind
Henrik
H
Lehnert
Mark
M
Mason
Ronald P
RP
Thurman
Ronald G
RG
Lemasters
John J
JJ
D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D001707:Biopsy, Needle; D005419:Flavonoids / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity
D005419:Flavonoids; D005609:Free Radicals; D010636:Phenols; D059808:Polyphenols; D000410:Alanine Transaminase