Heme oxygenase (HO) converts protoheme to biliverdin, which in turn is enzymatically metabolized to bilirubin . While HO-2 is constitutively expressed, HO-1 can be induced by its heme substrate as well as by heavy metals, oxidizing agents, and other environmental stresses. Tin protoporphyrin IX (SnPPIX) is a synthetic heme analog that selectively inhibits HO-1 (Ki = 11 nM) over HO-2 (IC50 = 7.5 μM). It also weakly inhibits endothelial nitric oxide synthase and soluble guanylyl cyclase (IC50s = 35 and 30 nM, respectively). SnPPIX prevents hyperbilirubinemia in neonates by blocking HO-1 activity that increases postnatally. It is rapidly cleared from plasma and persists in certain tissues, including kidney, liver, and spleen. SnPPIX is commonly used as a tool to study the role of HO-1 activity in cells and in animals.
