The protective properties of synthetic porphyrin tin complexes in toxic hyperbilirubinemia

Tin complexes of meso-substituted synthetic porphyrins, namely Sn4+ -meso-t etraphenyl-porphyrin (Sn-TPP) and Sn4+-meso-tetrakis(N-methyl-3-pyridyl)por phyrin tetratosylate (Sn-TMe-3-PyP), efficiently decrease the serum bilirub in level when injected subcutaneously at a dose of 100 mu M kg(-1) body wei ght into mice. These compounds are active during hyperbilirubinemia, induce d by phenylhydrazine, hemin and tetrachloromethane, and also during autoimm une hemolytic anemia. In the latter case a decrease in serum bilirubin cont ent was observed, as well as a decrease in the amount of blood reticulocyte s which reflects a milder course of the disease. The Sn complexes under stu dy induce, in vivo, cytochrome P-450, inhibit microsomal heme oxygenase and decrease the intensity of lipid peroxidation. At the same time, in vitro t he hepatic and splenic heme oxygenase activity is blocked only when a 0.1 m u M concentration of Sn-TMe-3-PyP or Sn-protoporphyrin IX is added to the i ncubation mixture. Sn-TPP does not affect the activity of this enzyme in vi tro. Copyright (C) 2000 John Wiley & Sons, Ltd.