Age-dependent sensitivity of cultured rat glial cells to bilirubin toxicity

The results of studies conducted in neural tissues and neuronal cell lines suggest that bilirubin is toxic to various cellular functions. Using stable bilirubin solutions and primary cultures of fetal rat glial cells we report on the toxic effects of bilirubin on cell morphology, cell viability, and mitochondrial function. Glial cells in culture exhibit age-in-culture-dependent sensitivity to bilirubin toxic effects. Between the ages of 2 and 12 days in vitro, a gradual tolerance to bilirubin developed. Bilirubin exposure resulted in 55, 22, and 5% decreases in mitochondrial function in 4-, 8-, and 12-day-old cells in culture, respectively. In addition, bilirubin toxicity was dependent on bilirubin-albumin molar ratio and bilirubin concentration and only partially dependent on length of exposure. The age-dependent phenomenon raises concern regarding the potential toxicity associated with exposure of premature neural cells to bilirubin.