The use of metalloporphyrins for the chemoprevention of neonatal jaundice.
Decreasing bilirubin formation is an important strategy for the prevention of neonatal jaundice. The stannic porphyrins, in particular tin protoporphyrin and tin mesoporphyrin, have been proposed for this purpose because these compounds competitively inhibit heme oxygenase, the rate-limiting enzyme in the heme-degrading pathway. However, these compounds are not only potent inhibitors of heme oxygenase but are also photosensitizers, which can generate cytotoxic oxygen species, such as singlet oxygen. Therapeutic regimens designed to avoid the phototoxicity caused by these and other metalloporphyrins have been suggested. An alternative approach would be the development of derivatives of tin protoporphyrin or other heme analogs that are less phototoxic and are stronger inhibitors of heme oxygenase. However, our understanding of the molecular basis of heme oxygenase inhibition is still limited. The response of heme oxygenase to specific inhibitors varies a great deal and depends on the organ and stage of development. This may be a result of the differing proportions of heme oxygenase isoenzymes in different organs. These questions and others need to be systematically answered so we may better understand and treat disturbances in heme homeostasis. In addition, administration of these compounds may have other metabolic consequences directly and indirectly related to their potent, long-lasting inhibition of heme oxygenase. The significance of such effects, whether transient or permanent, needs to be elucidated.
Stevenson
D K
DK
Department of Pediatrics, Stanford University School of Medicine, CA 94305-5119.
Rodgers
P A
PA
Vreman
H J
HJ
D001663:Bilirubin / Q000096:biosynthesis; D006418:Heme / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000378:metabolism / Q000517:prevention & control*; D008665:Metalloporphyrins / Q000627:therapeutic use*
D008665:Metalloporphyrins; D006418:Heme; D001663:Bilirubin