Sn-protoporphyrin inhibition of fetal and neonatal brain heme oxygenase. Transplacental passage of the metalloporphyrin and prenatal suppression of hyperbilirubinemia in the newborn animal.
Sn(tin)-protoporphyrin, a potent competitive inhibitor of heme oxygenase, can suppress hyperbilirubinemia in animal neonates and significantly reduce plasma bilirubin levels in animals and man. To further explore the biological actions and metabolic disposition of Sn-protoporphyrin, we have examined its effect in the suckling neonate when administered to the mother either 24-48 h before or immediately after birth. Sn-protoporphyrin, when administered before birth, crossed the placental membranes, inhibited fetal heme oxygenase, and suppressed the transient hyperbilirubinemia that occurs in the neonate after birth in a dose-dependent manner. Tissue heme oxygenase activity in the neonate was also lowered in a dose-dependent manner. The blood-brain barrier of the neonate was permeable to Sn-protoporphyrin for a period of between 20-28 d of postnatal life. Sn-protoporphyrin, however, was not retained in brain, but left the brain space with a t1/2 of 1.7 d. In addition, Sn-protoporphyrin administered once at birth to neonates inhibited brain heme oxygenase in a dose-dependent manner. The results of this study demonstrate that Sn-protoporphyrin can cross the placental membranes, inhibit tissue heme oxygenase activity in the fetus, and can also, following such prenatal treatment, suppress the hyperbilirubinemia of the newborn animal.
D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier; D001921:Brain / Q000196:embryology / Q000201:enzymology*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006932:Hyperbilirubinemia / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange; D008665:Metalloporphyrins; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011166:Porphyrins / Q000494:pharmacology*; D011247:Pregnancy; D011524:Protoporphyrins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing)