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Protective Properties of Tin‐ and Manganese‐Centered Porphyrins Against Hydrogen Peroxide‐Mediated Injury in Rat Astroglial Cells
Author(s) -
Dwyer Barney E.,
Lu ShiYi,
Laitinen Jarmo T.,
Nishimura Robert N.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71062497.x
Subject(s) - heme oxygenase , superoxide dismutase , chemistry , heme , hydrogen peroxide , superoxide , reactive oxygen species , porphyrin , pharmacology , biochemistry , enzyme , biology
Tin‐mesoporphyrin (tin‐mp), a potent inhibitor of heme oxygenase, and manganese (III) tetrakis(1‐methyl‐4‐pyridyl)porphyrin (MnTMPyP), a potent superoxide dismutase mimetic, reduced H 2 O 2 toxicity in cultures of transformed rat astroglial cells if added 30 min before, or at the same time as, H 2 O 2 . Reduced toxicity was not observed if treatment was delayed for 60 min, the time by which H 2 O 2 was essentially eliminated from cultures. Coadministration of tin‐mp and MnTMPyP did not increase protection over either compound administered individually. Tin‐mp, but not MnTMPyP, was stable in culture. MnCl 2 was not protective, suggesting that protection by MnTMPyP was not dependent on manganous ion, a by‐product of MnTMPyP breakdown. Protection by tin‐mp and MnTMPyP was not associated with metalloporphyrin‐mediated induction of heme oxygenase‐1 or with changes in heme oxygenase‐2 on western blots. Whereas protective concentrations of tin‐mp did not have superoxide dismutase‐mimetic properties in vitro, protective concentrations of MnTMPyP partially inhibited heme oxygenase. The data support the hypothesis that heme oxygenase inhibition is protective against acute oxidative injury.