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

Abstract

Gunn rats have a congenital deficiency of bilirubin-uridine diphosphate glucuronyltransferase (B-UDP-GT) activity and are unable to glucuronidate bilirubin 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-small-bowel transplantation as well as kidney transplantation for Gunn rats in congenic combination and compared the effects of these procedures. Serum total bilirubin (TBil) levels significantly decreased from 7.84 +/- 0.24 mg/dl to 2.19 +/- 0.43 mg/dl 2 weeks after total-small-bowel transplantation (n = 12). Correlation of hyperbilirubinemia was roughly proportional to the length of the transplanted small bowel. There were no difference in metabolic correction between jejunal and ileal transplantation. Serum TBil levels significantly decreased from 7.83 +/- 0.21 mg/dl to 2.24 +/- 0.98 mg/dl 2 weeks after kidney transplantation (n = 5). In conclusion, small-bowel and kidney transplantation were effective in correcting metabolic abnormality in Gunn rats for the period of 4-6 months. Estimated total B-UDP-GT activity supplemented by small-bowel or kidney transplantation was about 1/5-1/4 of the minimal requirement for the complete normalization of serum total bilirubin levels.

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

“…Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al, 1999).…”

“…Although correction of the deficient enzymatic activity in the affected organ, that is, the liver, would be the most straightforward, expression within an ectopic tissue, different from the natural production site, is an attractive option for clearance of toxic metabolites from the circulation. Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al , 1999).…”

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

“…Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al, 1999).…”

“…Although correction of the deficient enzymatic activity in the affected organ, that is, the liver, would be the most straightforward, expression within an ectopic tissue, different from the natural production site, is an attractive option for clearance of toxic metabolites from the circulation. Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al , 1999).…”

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

“…Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al, 1999).…”

“…Although correction of the deficient enzymatic activity in the affected organ, that is, the liver, would be the most straightforward, expression within an ectopic tissue, different from the natural production site, is an attractive option for clearance of toxic metabolites from the circulation. Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al , 1999).…”

Sustained Reduction of Hyperbilirubinemia in Gunn Rats After Adeno-Associated Virus-Mediated Gene Transfer of Bilirubin UDP-Glucuronosyltransferase Isozyme 1A1 to Skeletal Muscle

“…Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al, 1999).…”

“…Although correction of the deficient enzymatic activity in the affected organ, that is, the liver, would be the most straightforward, expression within an ectopic tissue, different from the natural production site, is an attractive option for clearance of toxic metabolites from the circulation. Interestingly, transplantation of small bowel and kidney, which also express UDP-glucuronosyltransferase (UDPGT), was effective at reducing hyperbilirubinemia in Gunn rats, thus suggesting that expression of the enzyme in nonhepatic sites is sufficient for metabolic correction of the disease (Kokudo et al , 1999).…”