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Enzymatic Removal of Bilirubin Toxicity by Bilirubin Oxidase In Vitro and Excretion of Degradation Products In Vivo

1990; SAGE Publishing; Volume: 195; Issue: 1 Linguagem: Inglês

10.3181/00379727-195-43119

1535-3702

M Kimura, Yasuhiro Matsumura, T Konno, Yasuyuki Miyauchi, Hiroshi Maeda,

Methemoglobinemia and Tumor Lysis Syndrome

The toxic effects of the degradation products of bilirubin that were formed by reaction with bilirubin oxidase were investigated with the C 1300 mouse neuroblastoma cell line by examining the following parameters: growth inhibition, morphologic characteristics, membrane transport, DNA synthesis, and protein synthesis. The addition of bilirubin to the cells resulted in definite cytotoxic effects on all of these parameters in a dose-dependent fashion; the addition of bilirubin oxidase reversed the toxic effects on the C 1300 cells in vitro. Furthermore, we found that most of these enzymatic degradation products of bilirubin were excreted by the kidney into the urine in a few hours after intravenous injection of the degradation products; in contrast, no intact bilirubin was excreted. Thus, these findings suggest that hyperbilirubinemia in newborn infants (kernicterus) may be prevented by administering polyethylene glycol-conjugated bilirubin oxidase, with a longer plasma half-life which has been reported previously to oxidize bilirubin to its nontoxic components in the bloodstream.