Bilirubin-Oxidizing Activity in Rat Brain

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Abstract
Bilirubin may be cleared from the brain by transport across the blood-brain barrier and by a ‘sink effect’ into the cerebrospinal fluid. However, there is also evidence to suggest that bilirubin may be metabolized in the brain by a process of oxidation. The purpose of this study was to confirm the existence of bilirubin metabolism in the brain and to examine the possible contribution of such an activity to the bilirubin staining pattern characteristic of kernicterus. Mitochondrial membrane fractions were prepared in 0.32 M sucrose from whole rat brains as well as brain regions. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the mitochondrial suspension. Our results confirmed the existence of a bilirubin-metabolizing activity in brain mitochondrial membranes. This activity could be removed by heating the mitochondrial suspension and had a definable temperature and pH maxima. The rate of oxidation of bilirubin ranged from 109 to 164pmol/min/mg protein. There were significant differences between rat brain regions in the ability to oxidize bilirubin. However, these differences could not explain the kernicterus staining phenomenon, because the highest activities were found in brain regions which are more heavily stained in kernicterus. We conclude that bilirubin is metabolized by brain mitochondrial membranes at a rate that would appear to represent a biologically meaningful contribution to bilirubin clearance from the brain. In the present model, differences in such an activity between brain regions do not appear to be compatible with a kernicteric staining pattern.

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