PROTECTIVE PROPERTIES OF TIN-CENTERED AND MANGANESE-CENTERED PORPHYRINS AGAINST HYDROGEN PEROXIDE-MEDIATED INJURY IN RAT ASTROGLIAL CELLS

Tin-mesoporphyrin (tin-mp), a potent inhibitor of heme oxygenase, and manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), a po tent super oxide dismutase mimetic, reduced H2O2 toxicity in cultures of transformed rat astroglial cells if added 30 min before, or at the same time as, H2O2. Reduced toxicity was not observed if treatment was delayed for 60 min, the time by which H2O2 was essentially eliminated from cultures. Coadministration of tin-mp and MnTMPyP did not increas e protection over either compound administered individually. Tin-mp, b ut not MnTMPyP, was stable in culture, MnCl2 was not protective, sugge sting that protection by MnTMPyP was not dependent on manganous ion, a by-product of MnTMPyP breakdown. Protection by tin-mo and MnTMPyP was not associated with metalloporphyrin-mediated induction of heme oxyge nase-1 or with changes in heme oxygenase-2 on western blots. Whereas p rotective concentrations of tin-mp did not have superoxide dismutase-m imetic properties in vitro, protective concentrations of MnTMPyP parti ally inhibited heme oxygenase. The data support the hypothesis that he me oxygenase inhibition is protective against acute oxidative injury.