Zinc protoporphyrin administration for suppression of increased bilirubin production by iatrogenic hemolysis in rhesus neonates.
We studied the effect of intravenous zinc protoporphyrin (ZnPP) administration on total body carbon monoxide excretion (VeCO), (an index of heme degradation), blood carboxyhemoglobin level, plasma bilirubin level, and tissue homogenate heme oxygenase activity 24 hours after delivery of rhesus neonates treated at 12 hours of age with heat-damaged erythrocytes (32 mumol heme/kg birth weight). All neonates were delivered by cesarean section and received ampicillin and gentamicin to suppress intestinal flora. The control group (n = 4) was treated with saline solution and ZnPP solvent; the erythrocyte-treated control group (n = 4) received erythrocytes and ZnPP solvent; and two experimental groups received erythrocytes and one dose of 10 (n = 3) or 40 (n = 4) mumol ZnPP/kg body weight, respectively. At 24 hours, administration of erythrocytes alone doubled the VeCO (p less than 0.05), carboxyhemoglobin level, (p less than 0.05), and plasma total bilirubin level (p less than 0.05). Treatment with ZnPP, 40 mumol/kg body weight, caused a significant decrease in VeCO (p less than 0.05), carboxyhemoglobin (p less than 0.05), bilirubin (p less than 0.05), and spleen heme oxygenase (p less than 0.05). Treatment of the erythrocyte-loaded animals with ZnPP, 10 mumol/kg body weight, also significantly (p less than 0.05) lowered VeCO and spleen heme oxygenase activity but did not cause a significant lowering of blood carboxyhemoglobin or plasma bilirubin concentration. We conclude that ZnPP is an effective, dose-dependent in vivo inhibitor of heme oxygenase in the newborn rhesus with latrogenic hemolysis, and that it suppresses both bilirubin production and subsequent accumulation.
Vreman
H J
HJ
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Rodgers
P A
PA
Stevenson
D K
DK
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001663:Bilirubin / Q000096:biosynthesis*; D002248:Carbon Monoxide / Q000378:metabolism; D004912:Erythrocytes; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006461:Hemolysis; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000517:prevention & control*; D008253:Macaca mulatta; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011166:Porphyrins / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000627:therapeutic use*
D011166:Porphyrins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006418:Heme; D002248:Carbon Monoxide; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin