Bronze Baby Syndrome: An Animal Model

Abstract

ABSTRACT. We evaluated the appropriateness of an animal model for the bronze baby syndrome. Ligation of the common bile duct in adult Wistar rats induces an accumulation of porphyrins and copper in the liver and a 20% conversion of protoporphyrin IX into Cu(I1)-protoporphyrin IX. Upon irradiation of these animals with superblue lamps, the plasma content of Cu(I1)-protoporphyrin increases by about 30%. Cholestasis also increases the recovery of porphyrins in the urine, although light treatment of ligated rats further increases urinary porphyrin excretion. The spectroscopic changes induced by irradiation of sera of ligated rats are consistent with the formation of products that have the typical spectrum found in bronze baby syndrome patients, i.e. a reduced absorbance in the visible region and an increased absorption in near-UV and red spectral regions. The products responsible for the brown discoloration found in bronze baby syndrome seem to result from phototransformation of copper-porphyrins subsequent to an electron transfer between photoexcited bilirubin and the copper ion. who observed a newborn infant with a gray-brown discoloration after phototherapy for unconjugated hyperbilirubinemia. Subsequent reports (2-6) described the clinical aspects of this syndrome, whereas other studies attempted to clarify the biochemical mechanisms leading to BBS (7-9). In 1982, large amounts of porphyrins were demonstrated in sera of BBS patients (8). These were identified as Cu-uro-, Cu-copro-, and Cu-protoporphyrin (9). In addition, large amounts of porphyrins were detected in sera of adult and pediatric patients with cholestatic disorders (10). The proposed mechanism for the onset of BBS invokes, first, the presence of cholestasis, causing elevated copper and porphyrin concentrations in serum, and second, hyperbilirubinemia and phototherapy (9-1 1). Cu-porphyrins undergo photodestruction, sensitized by bilirubin, to products that have generalized absorption in the near UV and red spectral regions and therefore are responsible for the brown discoloration (9-1 1).To shed further light on the mechanisms of development of this syndrome, we evaluated an animal model of BBS using Wistar rats subjected to ligation of the common bile duct. This strain of animals was chosen because in preliminary experiments we observed a consistent serum level of both conjugated and unconjugated bilirubin after common bile duct ligation. The results of these experiments were similar with those obtained by using heterozygous Gunn rats (12). MATERIALS AND METHODSChemicals. Bilirubin IX was purchased from Serva (Heidelberg, FRG) and used without further purification. Its concentration was evaluated by absorbance measurements at 460 nm using a molar extinction coefficient 164 000 M-' cm-' (ethanol solution) (13). All the free base porphyrins used were obtained from Porphyrin Products (Logan, UT) and converted into their Cu(I1) derivatives by reaction with cupric acetate (14). SDS was the product of Merck (Darmstadt, FRG). All other chemicals were comm...

Age-Dependent Reference Values of Urinary Porphyrins in Children

“…Compared with our newly established reference values for the new-born group, all three porphyrins were elevated significantly which indicated a bronze baby syndrome in this patient. This finding was consistent with the abnormal porphyrin levels determined by other authors in blood from a patient and from an animal model with the same disorder (13,14). There was no disturbance of porphyrin metabolism in the parents of the affected baby, as their urinary, faecal and erythrocytic porphyrins were all normal.…”

Porphyrin-Induced Photooxidation of Conjugated Bilirubin

“…The present results and kinetic results have ruled out the possibility that bilirubin-induced photooxidation of porphyrins should occur in Bronze Baby Syndrome sera [18,19].…”

“…Neonatal serum contains a high concentration of bilirubin, abnormal concentration of copper and porphyrins (UP and coproporphyrin) [18,19].…”

“…Large amounts of porphyrins and abnormal concentrations of copper are found in neonatal hyperbilirubinaemia patient serum [18,19]. Irradiation of bilirubin in vitro elicits the oxidation of bilirubin [9] and the photooxidation of bilirubin is markedly increased in the presence of photosensitizers [12,14,20].…”

Cutaneous porphyria in a neonate with tyrosinaemia type 1

“…Skin toxicity due to secondary porphyria in the neonate is well documented in the bronze baby syndrome but its presentation is very dierent. Interactions between photoactivated conjugated bilirubin and copper-porphyrins lead to a bronze discolouration rather than to a purpura, with an excess of proto-, copro-and uroporphyrins [2,11]. Recently, porphyrinaemia due to cholestasis was proposed as one causative factor of`purpuric phototherapy-induced eruptions' and of`bullous eruptions' in three neonates described in two dierent reports [5,10].…”