Studies of cellular toxicity of unconjugated bilirubin in kernicteric brain.

Intracerebral deposition of unconjugated bilirubin is believed to be primarily responsible for the neurological manifestations of kernicterus1 (1). Numerous in vitro studies have been carried out on the effect of unconjugated bilirubin on metabolic activity of liver and brain mitochondria (2), brain homogenates (3), cells grown in tissue culture (4, 5), and unicellular organisms (6). The majority of these investigations have shown that the pigment depresses oxygen consumption and, to a greater extent, the phosphorylation of these preparations (7). Accordingly, it has been postulated that unconjugated bilirubin exerts its cytotoxic effect in kernicteric brain by uncoupling phosphorylation from oxidation (7), with resultant decrease in synthesis of adenosine triphosphate (ATP) and subsequent impairment of energy-dependent cerebral metabolism. An in vivo assessment of this concept has been carried out in the present investigation. Oxygen consumption and ATP concentration have been measured in the brain of kernicteric Gunn rats,