Effects of luminal nutrients and small bowel transplants on congenital indirect hyperbilirubinemia.
The Gunn rat is an excellent model of Crigler-Najjar syndrome, type 1. In previous studies we demonstrated that heterotopic 15-20-cm jejunal transplants from Wistar rats lowered serum bilirubin levels by 40%, and the reduction was transient (6 weeks). In contrast, orthotopic transplants decreased bilirubin levels by 60% and the effect persisted throughout the 8-week study. This study was initiated to identify the luminal substance(s) which are responsible for the persistent bilirubin-lowering effect of jejunal transplants. Thirty-one Wistar to Gunn 15-20-cm jejunal transplants were randomized to receive daily Thiry-Vella graft irrigation with 5 ml of normal saline (n = 8); bile salts (cholate + deoxycholate, 40 mg/ml, n = 5; fats (Microlipid, 20 mg/ml, n = 5); proteins (Casec caseinate, 40 mg/ml, n = 5); and sugars (Moducal + Polycose, 40 mg/ml, n = 8). Bilirubin levels were measured spectrophotometrically at weekly intervals. At 4 and 8 weeks, enzyme-induced bilirubin conjugation activity was measured using added known amounts of added bilirubin. Irrigation of the transplants with saline, protein, and sugar resulted in moderate (40%) lowering of serum total and indirect bilirubin levels. Fat was significantly more effective, lowering mean total bilirubin levels from 9.6 +/- 0.4 to 1.6 +/- 0.2 mg/dl at 6 weeks. After this time, bilirubin levels increased slightly. Bile salts were slightly less effective, lowering bilirubin levels at 6 weeks by only 75%. However, this effect persisted and at 8 weeks levels averaged 2.4 +/- 0.2 mg/dl. Conjugating enzyme activity in the transplants increased from 1.4 +/- 0.3 to 2.5 +/- 0.5 mg bilirubin conjugated/mg tissue/hr. Luminal fats and bile salts appear to augment enzyme-induced bilirubin conjugation in heterotopic jejunal transplant recipients.
Burgos
A A
AA
Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Martinez
M E
ME
Rajasekaran
M
M
Jaffe
B M
BM
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D001663:Bilirubin / Q000097:blood; D005766:Gastrointestinal Contents; D006933:Hyperbilirubinemia, Hereditary / Q000097:blood / Q000503:physiopathology* / Q000601:surgery*; D007583:Jejunum / Q000637:transplantation*; D008055:Lipids / Q000502:physiology; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D007507:Therapeutic Irrigation; D016042:Transplantation, Heterotopic
D001647:Bile Acids and Salts; D008055:Lipids; D001663:Bilirubin