The use of metalloporphyrins for the chemoprevention of neonatal jaundice
D. K. Stevenson, P. A. Rodgers and H. J. Vreman
Department of Pediatrics, Stanford University School of Medicine, CA 94305-5119.
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.
