title: The effects of bilirubin on brain energy metabolism during normoxia and hypoxia: an in vitro study using 31P nuclear magnetic resonance spectroscopy.
abstract: Available evidence from in vitro studies suggests that the neurotoxic effects of bilirubin may be exacerbated by, or even require, additional factors such as hypoxia or asphyxia. The aim herein was to use 31P nuclear magnetic resonance spectroscopy to study the effects of bilirubin on brain energy metabolism in vitro under conditions of normoxia and hypoxia. 31P nuclear magnetic resonance spectra were acquired from guinea pig cerebral hemisphere slices during superfusion with solutions containing bilirubin and albumin in 5:1 molar ratio. The effects of bilirubin at concentrations between 400 nmol/liter and 120 mumol/liter were studied under normoxic conditions. Bilirubin caused no apparent disruption in brain energy metabolism during normoxia. The combined effects of bilirubin (40 mumol/liter) and hypoxia were studied. Hypoxia alone led to a steady state reduction in the phosphocreatine to inorganic phosphate peak-height ratio to 0.30 (0.27-0.32) [mean (range) n = 3]. Bilirubin (40 mumol/liter) in the presence of hypoxia caused a further reduction in the phosphocreatine to inorganic phosphate ratio to 0.18 (0.17-0.20) [mean (range) n = 3, p less than 0.01, analysis of variance] which was rapidly reversed on returning to normoxia. These results demonstrate that bilirubin at the concentration studied requires hypoxia, in addition, to cause a measurable disturbance of brain energy metabolism. The nature of this interaction is unknown, but it may reflect the effect of intracellular acidosis on bilirubin solubility or the oxygen dependence of brain mitochondrial bilirubin oxidase.
authors.affiliation: Department of Paediatrics, School of Medicine, University College, Rayne Institute, London, England.
authors.forename: N K
authors.initials: NK
authors.lastname: Ives
authors.forename: D W
authors.initials: DW
authors.lastname: Cox
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
authors.forename: H S
authors.initials: HS
authors.lastname: Bachelard
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis
chemical_list: D000418:Albumins; D010710:Phosphates; D010725:Phosphocreatine; D001663:Bilirubin; D010100:Oxygen