Effects of endotoxemia and sepsis on bilirubin oxidation by rat brain mitochondrial membranes.
Sepsis is believed to increase the risk of bilirubin brain toxicity, but the mechanism is not known. Adult male Sprague-Dawley rats were injected intraperitoneally with either 20 mg/kg Escherichia coli lipopolysaccharide, approximately 5 x 10(9)/kg CFU Listeria monocytogenes or vehicle 48 h prior to sacrifice. Rats were killed with an intraperitoneal injection of pentobarbital. Mitochondrial membrane fractions were produced by homogenization of the brains and differential centrifugation in 0.32 M sucrose. The mitochondrial pellet was resuspended in distilled water and sonicated to rupture the mitochondria. The protein concentration 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 10 microM bilirubin, 5 mM EDTA, and 500 U/ml catalase. Optical density was measured at 440 nm before and after a 60-min incubation at 37.5 degrees 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 involve other mechanisms.
Allen
J W
JW
Department of Anesthesia and Critical Care Medicine, University of Pittsburgh, Children's Hospital of Pittsburgh, USA.
Tommarello
S
S
Carcillo
J
J
Hansen
T W
TW
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D019446:Endotoxemia / Q000378:metabolism*; D004926:Escherichia coli; D007425:Intracellular Membranes / Q000378:metabolism*; D007647:Kernicterus / Q000209:etiology; D008089:Listeria monocytogenes; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D018805:Sepsis / Q000378:metabolism*
D001663:Bilirubin