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Characterization of LY231617 Protection Against Hydrogen Peroxide Toxicity
Author(s) -
Fuson Kimberly S.,
Mark Robert J.,
Panetta Jill A.,
May Patrick C.
Publication year - 1999
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.1471-4159.1999.0721154.x
Subject(s) - glutathione , cytoprotection , toxicity , chemistry , hydrogen peroxide , pharmacology , oxidative stress , antioxidant , lactate dehydrogenase , in vivo , neuroprotection , biochemistry , enzyme , medicine , biology , microbiology and biotechnology , organic chemistry
: The compound LY231617{2,6‐bis(1,1‐dimethylethyl)‐4‐[[(1‐ethyl)amino]methyl]phenol hydrochloride}has been reported to afford significant neuroprotection against hydrogenperoxide (H 2 O 2 )‐induced toxicity in vitro and globalischemia in vivo. We now report on further mechanistic studies ofH 2 O 2 toxicity and protection by LY231617. Brief exposureto H 2 O 2 (15 min) elicited an oxidative insult comparablewith that generated by overnight treatment.H 2 O 2 ‐mediated cellular degeneration was characterizedusing lactate dehydrogenase (LDH) release, changes in total glutathione, and anew marker of oxidative stress, 8‐epiprostaglandin F 2α (8‐isoprostane). LY231617 attenuated H 2 O 2 ‐mediateddegeneration under a variety of exposure conditions, including a moreclinically relevant posttreatment paradigm. Levels of 8‐isoprostane paralleledLDH release under various treatment paradigms of 100 μ M H 2 O 2 ± 5 μ M drug. In contrast, despite affording significant protection, LY231617 had modest to no effects on cellular levels of glutathione. Taken together, these results are consistent with a membrane site of action for LY231617 and suggest that the compound affords cytoprotection via its antioxidant properties.