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Correction of congenital hyperbilirubinemia in homozygous Gunn rats by xenotransplantation of hamster livers

Wakizaka, Y and Miki, T and Rao, AS and Wang, X and Goller, AL and Demetris, AJ and Fung, JJ and Starzl, TE and Valdivia, LA (1997) Correction of congenital hyperbilirubinemia in homozygous Gunn rats by xenotransplantation of hamster livers. Xenotransplantation, 4 (4). 262 - 266. ISSN 0908-665X

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Abstract

The homozygous Gunn j/j rat is an animal model for Crigler-Najjar syndrome in which the lack of the enzyme uridine diphosphoglucoronate-glucuronosyltransferase (UDP-GT) results in congenital unconjugated nonhemolytic hyperbilirubinemia. Because the binding of bilirubin to albumin in plasma varies from species to species, xenotransplantation (XTx) of liver afforded in this model the opportunity to study the interactions between xenoproteins of the donor and bilirubin of the recipient. For this purpose, orthotopic liver transplantation (OLTx) was performed from hamster to adult Gunn j/j rats. No immunosuppression (IS) was given to controls (Group I, n=5) and to OLTx recipients of syngeneic (Gunn j/j rat) grafts (Group II, n=5), whereas tacrolimus (1 mg/kg/day × 15 days, IM) and cyclophosphamide (8 mg/kg/day × 7 days, IP) were administered to animals receiving hamster xenografts (Group III, n=11). While untreated animals (Group I) died within 7 days (6.8±0.2 days) post-transplantation (Tx), the use however of IS resulted in prolonged (30.2±6.8 days) survival of xenogeneic recipients (Group III) who eventually succumbed to rejection. A precipitous decline in total serum bilirubin (TBili) from pre-operative levels of 5.3±1.0 mg/dL to 0.5±0.2 mg/dL was noted in both Group I and III animals, an observation that sustained itself only in the latter group during the course of their follow-up. The decrease in TBili was also associated with a contemporaneous increase in biliary concentration of conjugated bilirubin. No noticeable reversal of hyperbilirubinemia was however observed in OLTx recipients of syngeneic grafts (Group II). Taken together, these data suggest that hamster albumin and hepatocyte-associated xenoproteins and enzymes involved in the process of membrane transport and glucuronidation of bilirubin, functioned efficaciously after OLTx in Gunn j/j rats, resulting in the reversal of the inborn error of metabolism for the duration of follow-up. © Munksgaard, Copenhagen.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wakizaka, Y
Miki, T
Rao, AS
Wang, X
Goller, AL
Demetris, AJ
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Valdivia, LA
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 November 1997
Date Type: Publication
Journal or Publication Title: Xenotransplantation
Volume: 4
Number: 4
Page Range: 262 - 266
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0908-665X
Other ID: uls-drl:31735062127810, Starzl CV No. 2060
Date Deposited: 08 Apr 2010 17:35
Last Modified: 13 Oct 2017 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/5446

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