EFFECTS OF ENDOTOXEMIA AND SEPSIS ON BILIRUBIN OXIDATION BY RAT-BRAINMITOCHONDRIAL-MEMBRANES

Sepsis is believed to increase the risk of bilirubin brain toxicity, b ut the mechanism is not known, Adult male Sprague-Dawley rats were inj ected intraperitoneally with either 20 mg/ kg Escherichia coil lipopol ysaccharide, approximate to 5 x 10(9)/kg CFU Listeria monocytogenes or vehicle 48 h prior to sacrifice, Rats were killed with an intraperito neal injection of pentobarbital. Mitochondrial membrane fractions were produced by homogenization of the brains and differential centrifugat ion in 0.32 M sucrose, The mitochondrial pellet was resuspended in dis tilled water and sonicated to rupture the mitochondria. The protein co ncentration of the suspension was standardized to 2.5 mg/ml. Bilirubin oxidation was assayed in a pH 8.2, 0.1 M barbital buffer containing 1 0 mu M bilirubin, 5 mM EDTA, and 500 U/ml catalase, Optical density wa s measured at 440 nm before and after a 60-min incubation at 37.5 degr ees C. There were no differences between the control, endotoxemic, and septic groups as far as the ability of brain mitochondrial membranes to oxidize bilirubin (bilirubin oxidation rate: 289 +/- 11 vs. 295 +/- 9 vs. 296 +/- 12 pmol/min/mg protein, mean +/- SD). We conclude that endotoxemia or sepsis do not change the ability of brain mitochondrial membranes to oxidize bilirubin, If sepsis truly increases the risk of bilirubin encephalopathy in neonatal jaundice, this is likely to invo lve other mechanisms.