Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention by plant polyphenols.
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.[1]References
- Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention by plant polyphenols. Zhong, Z., Connor, H.D., Froh, M., Bunzendahl, H., Lind, H., Lehnert, M., Mason, R.P., Thurman, R.G., Lemasters, J.J. Gastroenterology (2005) [Pubmed]
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