Be. Dwyer et al., PROTECTIVE PROPERTIES OF TIN-CENTERED AND MANGANESE-CENTERED PORPHYRINS AGAINST HYDROGEN PEROXIDE-MEDIATED INJURY IN RAT ASTROGLIAL CELLS, Journal of neurochemistry, 71(6), 1998, pp. 2497-2504
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.