Oxidation of Bilirubin by Rat Brain Mitochondrial Membranes—Genetic Variability

Abstract

Bilirubin is oxidized by brain mitochondrial membranes at a rate which may contribute significantly to clearance of bilirubin from brain. Different strains of congenitally jaundiced rats (Gunn rats) vary widely as far as the mortality rate of the homozygous (jaundiced) pups. Because the ability to oxidize bilirubin in brain may protect against toxicity, we hypothesized that the ability to oxidize bilirubin would be lower in Gunn rat strains (ACI/N-j) with a high mortality rate in the homozygous pups. Mitochondria were obtained from young rat brains by differential centrifugation in sucrose gradients. The mitochondria were ruptured by sonication. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the membrane suspension. The rate of bilirubin oxidation was significantly lower in rats of the RHA/N-j strain both at 7–8 days of age and in adults, compared to rats of the ACI/N-j and the Sprague-Dawley strains at the same age points. Differences in mortality rates between the RHA/N-j and the ACI/N-j strains of Gunn rats could not be explained on the basis of differences in the ability of brain mitochondrial membranes to oxidize bilirubin, as these activities were lower in the RHA/N-j rats, which also have lower mortality rates, but higher in the ACI/N-j rats, which have remarkably high mortality rates. This study also confirmed previous findings relative to age maturation of the enzyme activity.