BILIRUBIN-OXIDIZING ACTIVITY IN RAT-BRAIN

Bilirubin may be cleared from the brain by transport across the blood- brain barrier and by a 'sink effect' into the cerebrospinal fluid. How ever, there is also evidence to suggest that bilirubin may be metaboli zed 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 biliru bin staining pattern characteristic of kernicterus. Mitochondrial memb rane fractions were prepared in 0.32 M sucrose from whole rat brains a s well as brain regions. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the mi tochondrial suspension, Our results confirmed the existence of a bilir ubin-metabolizing activity in brain mitochondrial membranes, This acti vity could be removed by heating the mitochondrial suspension and had a definable temperature and pH maxima. The rate of oxidation of biliru bin ranged from 109 to 164 pmol/min/mg protein, There were significant differences between rat brain regions in the ability to oxidize bilir ubin, However, these differences could not explain the kernicterus sta ining phenomenon, because the highest activities were found in brain r egions which are more heavily stained in kernicterus, We conclude that bilirubin is metabolized by brain mitochondrial membranes at a rate t hat would appear to represent a biologically meaningful contribution t o bilirubin clearance from the brain, In the present model, difference s in such an activity between brain regions do not appear to be compat ible with a kernicteric staining pattern.