Amit Y, Chan G, Fedunec S, Poznansky M J, Schiff D
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Pediatr Res. 1989 Apr;25(4):364-8. doi: 10.1203/00006450-198904000-00010.
Though bilirubin is reported to affect a variety of cellular functions, the primary target of its toxic effect is still not known. A major problem in understanding this is the wide variation in results reported by different groups. This is probably due to the differences in stability of bilirubin solutions arising from large differences in bilirubin:albumin molar ratios used in experiments. Hence in studying the toxic effects of bilirubin in tissue culture systems, it is important to be certain that the bilirubin is maintained in solution throughout the time of the exposure to bilirubin. Spectrophotometric measurements have shown that bilirubin is stable in Dulbecco's modified Eagle medium solution at bilirubin:albumin molar ratios up to 3. Under these defined conditions, bilirubin was found to affect Na+K+ ATPase, [3H]-thymidine uptake, L-[35S]methionine incorporation into protein and mitochondrial function at bilirubin concentrations up to 125 microM and bilirubin:albumin molar ratio of 1.5. Toxic effects on all parameters measured were evident at bilirubin:albumin molar ratio of 1.5 after a minimum of 2 h of exposure. No effect was evident at a bilirubin:albumin molar ratio below 1. Although it is not possible to identify with certainty the primary target, the effect on mitochondrial function appeared earlier and was more profound than that seen with the other assessed functions.
尽管据报道胆红素会影响多种细胞功能，但其毒性作用的主要靶点仍不清楚。理解这一点的一个主要问题是不同研究小组报告的结果差异很大。这可能是由于实验中使用的胆红素与白蛋白摩尔比差异很大，导致胆红素溶液稳定性不同。因此，在研究组织培养系统中胆红素的毒性作用时，重要的是要确保在整个胆红素暴露期间，胆红素都能保持在溶液中。分光光度测量表明，在胆红素与白蛋白摩尔比高达3的情况下，胆红素在杜尔贝科改良伊格尔培养基溶液中是稳定的。在这些确定的条件下，发现胆红素在浓度高达125微摩尔、胆红素与白蛋白摩尔比为1.5时，会影响钠钾ATP酶、[3H]胸苷摄取、L-[35S]甲硫氨酸掺入蛋白质以及线粒体功能。在暴露至少2小时后，在胆红素与白蛋白摩尔比为1.5时，对所有测量参数的毒性作用都很明显。在胆红素与白蛋白摩尔比低于1时，没有明显影响。虽然无法确定主要靶点，但对线粒体功能的影响出现得更早，且比其他评估功能所见的影响更显著。
