Conjugation and Excretion of Bilirubin

Chowdhury, Jayanta Roy; Chowdhury, Namita Roy

doi:10.1055/s-2008-1040667

Cited by 17 publications

(9 citation statements)

References 12 publications

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“…However, Tx of livers across xenogeneic barriers may raise the possibility of metabolic incompatibilities necessitating their careful delineation. To address this issue, we transplanted hamster livers into homozygous Gunn rats, in whom the absence of the enzyme UDP-GT results in the manifestation of unconjugated nonhemolytic hyperbilirubinemia [5][6][7]. Since there is no variability of the bilirubin molecule among different species [8], it is expected that its process of membrane transport and glucuronidation would proceed unabatedly after liver xenotransplantation.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is not clear if these proteins would interact adequately with proteins or other molecules of the recipient thus mitigating interspecies incompatibilities. In an attempt to address this issue pragmatically, we resorted to transplanting hamster livers into adult Gunn j/j , rats; an animal model of Crigler-Najjar syndrome, in which due to the absence of enzyme UDP-GT, a rare form of autosomal recessive congenital unconjugated hyperbilirubinemia, is observed [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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

Wakizaka

Miki

Rao

et al. 1997

Xenotransplantation

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The homozygous Gunn j/j rat is an animal model for Crigler-Najjarsyndrome 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=l1). 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 followup.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wakizaka

Miki

Rao

et al. 1997

Xenotransplantation

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“…We had a small number of patients with documented injuries from which to draw conclusions. Additionally, blunt abdominal trauma patients may suffer from hypovolemic shock, which may have reduced renal perfusion and thus urine output leading to false negative results 2. Furthermore, we did not assess the effects of prerenal azotemia and metabolic acidosis on the metabolism of bilirubin and urobilinogen.…”

Section: Limitationsmentioning

confidence: 99%

“…Multiple studies in the emergency medicine (EM) and pathology literature in the late 1980s showed a quantitative correlation between urobilinogen and serum liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] that demonstrated urobiliogen as a useful screening marker of liver dysfunction in non-trauma medical patients presenting to the emergency department (ED) 1,2. The presence of urine bilirubin is described as highly specific for elevated serum bilirubin due to hepatocellular or biliary tree injury, rather than intravascular hemolysis 1,2.…”

Section: Introductionmentioning

confidence: 99%

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75: Analysis of Urobilinogen and Urine Bilirubin for Intra-abdominal Injury in Blunt Trauma Patients

Gorchynski

Dean

Anderson

2008

Annals of Emergency Medicine

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Objective: To determine the point prevalence of urine bilirubin, urine hemoglobin and urobilinogen in blunt trauma patients, and to evaluate its utility as a screening tool for intra-abdominal injury.Methods: Data analysis of 986 consecutive trauma patients of which 698 were adult blunt trauma patients. Five-hundred sixteen subjects had a urinalysis and a CT scan of the abdomen/pelvis or exploratory laparotomy. We reviewed initial urinalysis results from trauma patients in the emergency department (ED) for the presence of urine hemoglobin, uroblinogen and urine bilirubin. Computed tomography (CT) scan results and operative reports were reviewed from the trauma registry for evidence of liver laceration, spleen laceration, bowel or mesenteric injuries.Results: There were 73 injuries and 57/516 patients (11%) with intra-abdominal injury. Urinalysis was positive for urobilinogen in 28/516 (5.4%) patients, urine bilirubin in 15/516 (2.9%) patients and urine hemoglobin in 313/516 (61%) patients. Nineteen/forty-seven (4%) subjects had liver lacerations, 28/56 (5%) splenic lacerations, and 15/5 (3%) bowel or mesenteric injury. Comparing the proportion of patients that had urobilinogen detected in the group with and without intra-abdominal injury, 8/28 (29%) subjects with urobilinogen, 5/15 (33%) subjects with bilirubin and 47/313 (15%) subjects with urine hemoglobin were found to have liver lacerations, spleen lacerations, or bowel/mesenteric injuries. Preexisting liver or biliary conditions were not statistically associated with elevation of urine bilirubin, urine hemoglobin or urobilinogen on initial urinalysis after blunt abdominal trauma. Point prevalence for urobilinogen, urine bilirubin and urine hemoglobin are 5.43% (28/516), 2.91% (15/516) and 60.7% (313/516) respectively.

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Prenatal Diagnosis of Bilirubin–Udp–Glucuronosyltransferase Deficiency in Rats by Genomic Dna Analysis

et al. 1992

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Hepatic bilirubin excretion requires UDP-glucuronosyltransferase-mediated glucuronidation. Patients with type I Crigler-Najjar syndrome and mutant rats (Gunn strain) inherit deficiency of UDP-glucuronyltransferase activity toward bilirubin as an autosomal recessive trait and, as a result, exhibit marked nonhemolytic unconjugated hyperbilirubinemia throughout postnatal life. Heterozygous carriers of the trait have normal serum bilirubin levels. Because of placental excretion of unconjugated bilirubin, type 1 Crigler-Najjar syndrome patients and Gunn rats are not jaundiced in utero, making prenatal diagnosis difficult. Here we report a diagnostic method in Gunn rats based on genomic DNA analysis for prenatal recognition of deficiency of UDP-glucuronyltransferase activity toward bilirubin in Gunn rats and identification of heterozygous carriers. We and others have shown that two distinct messenger RNA species (UDP-glucuronyltransferase activity toward bilirubin and the 3-methylcholanthrene-inducible phenol-UDP-glucuronyltransferase messenger RNA) in Gunn rat liver contain identical deletions of a single guanosine residue in their common 3' regions. Loss of the restriction site for the endonuclease BstNI, which results from this deletion, was used as the basis for a diagnostic test. Female heterozygous Gunn rats were mated with male homozygous Gunn rats. Genomic DNA was extracted from the chorionic aspect of placenta of 17-day fetuses or from leukocytes from normal rats, obligate heterozygotes and homozygous Gunn rats. The DNA was sequentially digested with the restriction enzymes EcoRI and BstNI and subjected to Southern-blot analysis with a double-stranded DNA probe for the common region of UDP-glucuronyltransferase activity toward bilirubin and the 3-methylcholanthrene-inducible UDP-glucuronyltransferase messenger RNAs.(ABSTRACT TRUNCATED AT 250 WORDS)

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Conjugation and Excretion of Bilirubin

Cited by 17 publications

References 12 publications

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

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

75: Analysis of Urobilinogen and Urine Bilirubin for Intra-abdominal Injury in Blunt Trauma Patients

Prenatal Diagnosis of Bilirubin–Udp–Glucuronosyltransferase Deficiency in Rats by Genomic Dna Analysis

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