Abstract
Introduction: Metalloporphyrins, competitive heme oxygenase (HO) inhibitors, may potentially be used as drugs for preventing neonatal hyperbilirubinemia. Metalloporphyrins that specifically target the inducible HO-1 without inhibiting the constitutive HO-2 are the most ideal. Zinc protoporphyrin (ZnPP) has the most promise. We have derived a plant-based ZnPP (ZnPP-Plant) and evaluated its inhibitory potency and selectivity for the HO-1 isozyme. METHODS: Eleven-µM ZnPP-Plant or technical grade ZnPP (ZnPP-TG) were added to reaction vials containing heme, NADPH, and adult mouse spleen, brain, and liver sonicates. Gas chromatography was used to measure total in vitro HO activity in sonicates. Percent inhibition of control HO activity was then compared. RESULTS: At a 11-µM concentration, ZnPP-Plant and ZnPP-TG inhibited HO activity in the liver (69.7 ± 9.3% and 74.2 ± 10.3%, respectively); spleen (65.8 ± 17.9% and 46.8 ± 8.7%, respectively); and brain (54.1 ± 13.3%, and 38.1 ± 13.9%, respectively). CONCLUSION: ZnPP-Plant has equal inhibitory potency as ZnPP-TG, and thus has potential use for treating neonatal hyperbilirubinemia.
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