Supplement of liver enzyme by intestinal and kidney transplants in congenitally enzyme-deficient rat

Gunn rats have a congenital deficiency of bilirubin-uridine diphosphate glu curonyltransferase (B-UDP-GT) activity and are unable to glucuronidate bili rubin in the bile, resulting in unconjugated hyperbilirubinemia. Other than the liver, several organs, including small bowel and kidneys, are known to have B-UDP-GT activity in normal rats. We performed total- or partial-smal l-bowel transplantation as well as kidney transplantation for Gunn rats in congenic combination and compared the effects of these procedures. Serum to tal bilirubin (TBil) levels significantly decreased from 7.84 +/- 0.24 mg/d l to 2.19 +/- 0.43 mg/dl 2 weeks after total-small-bowel transplantation (n = 12). Correlation of hyperbilirubinemia was roughly proportional to the l ength of the transplanted small bowel. There were no difference in metaboli c correction between jejunal and ileal transplantation. Serum TBil levels s ignificantly decreased from 7.83 +/- 0.21 mg/dl to 2.24 +/- 0.98 mg/dl 2 we eks after kidney transplantation (n = 5). In conclusion, small-bowel and ki dney transplantation were effective in correcting metabolic abnormality in Gunn rats for the period of 4-6 months. Estimated total B-UDP-GT activity s upplemented by small-bowel or kidney transplantation was about 115-1/4 of t he minimal requirement for the complete normalization of serum total biliru bin levels. (C) 1999 Wily-Liss, Inc.