Protective properties of tin- 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 potent superoxide 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 increase protection over either compound administered individually. Tin-mp, but not MnTMPyP, was stable in culture. MnCl2 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.
Dwyer
B E
BE
Molecular Neurobiology Laboratory (151), Department of Veterans Affairs Medical Center, White River Junction, Vermont 05009-0001, USA.
Lu
S Y
SY
Laitinen
J T
JT
Nishimura
R N
RN
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000648:ultrastructure; D002461:Cell Line, Transformed; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D008854:Microscopy, Electron; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D014001:Tin / Q000494:pharmacology*
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D011166:Porphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D008345:Manganese; D014001:Tin; D006861:Hydrogen Peroxide