Effect of stobadine, U-74389G, trolox and melatonin on resistance of rat hippocampal slices to oxidative stress.
Reactive oxygen species have been suggested to participate in the impairment of nervous tissue by oxidative stress, induced by hypoxia (HYP) followed by reoxygenation (ROX). Although the mechanisms of such injury are rather complex, antioxidants might exert some protective action under such circumstances. This study tested the effect of a series of compounds interfering with the generation and action of reactive oxygen species on impairment of synaptic transmission in the CA1 region of rat hippocampal slices exposed to HYP followed by ROX in vitro. Shortlasting HYP (typically 4.5-7.5 min under the conditions used) resulted in fast decay of the amplitude of population spikes evoked in the CA1 neurons by stimulation of Schäffer collaterals. The impairment was mostly irreversible. However, in the presence of the antioxidants stobadine, 21-aminosteroid U-74389G, melatonin and trolox (with optimal concentrations of 10-30 micromol/l, 10 micromol/l, 30-100 micromol/l and 200 micromol/l, respectively), the irreversible damage of the transmission was significantly diminished. The decay of the synaptic transmission failure during HYP was also delayed by stobadine, U-74389G and melatonin. The results demonstrated that compounds with antioxidant activity may effectively protect nervous tissue during HYP and ROX.
Vlkolinský
R
R
Institute of Experimental Pharmacology, Slovak Academy of Sci., Bratislava, Slovak Republic.
Stolc
S
S
Ross
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D000975:Antioxidants; D002243:Carbolines; D002839:Chromans; D018696:Neuroprotective Agents; D011281:Pregnatrienes; C074965:U 74389F; D008550:Melatonin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C100106:dicarbine