Protective effect of stobadine, a pyridoindole antioxidant, in hypoxia-reoxygenation injury of ganglionic and hippocampal neurotransmission.
Hypoxia (HYP) followed by reoxygenation (REOX) occurs frequently in the pathophysiology of the CNS. Free oxygen radicals (FOR) may participate in cerebral injury under such circumstances. Pharmacological control of the generation and/or subsequent effects of FOR by new effective compounds might contribute to the treatment of disorders such as stroke and cerebral trauma. Effects of stobadine, a pyridoindole antioxidant that is able to interact with some FOR, were analyzed on synaptic transmission in rat superior cervical ganglia and hippocampal slices during HYP-REOX procedure in vitro. The amplitude of compound action potential in the ganglion evoked by supramaximal electrical stimulation of preganglionic nerve was reduced to approximately 20% of the control value during HYP (90 min). The action potential did not recover during REOX (60 min). Stobadine (10 mM) applied before, during, and after HYP, did not change the HYP-induced inhibition; however, a significant recovery of transmission (to 78.5% +/- 8.3) occurred during REOX. A similar effect was observed in the presence of the antioxidant Trolox (0.2 mM), a derivative of alpha-tocopherol. Stobadine, in concentrations of > 30 microM inhibited ganglionic transmission in a concentration-dependent manner. HYP lasting more than 2-3 min fully depressed field action potentials evoked in hippocampal CA1 region neurons by supramaximal electrical stimulation of Schäffer collaterals. If HYP exceeded 8 min, transmission did not recover during REOX. Stobadine (10 microM) applied during HYP significantly enhanced the probability of transmission recovery in the REOX period. Some preparations recovered following HYP lasting as long as 13-15 min. On applying the compound before, during, and after HYP that lasted for 8 min, the transmission recovery was 72.6% +/- 21.8 of the control value, compared to only 16.1% +/- 12.7 in the untreated preparations. In concentrations ranging from 0.3-1.73 mM, stobadine inhibited hippocampal transmission. Stobadine proved to be an effective agent in the protection of synaptic transmission against HYP-REOX-induced injury in both neuronal preparations studied in vitro. This effect might be linked to the antioxidant and free radical scavenging effects of stobadine.
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
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Selecká
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002243:Carbolines / Q000627:therapeutic use*; D002839:Chromans / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000975:Antioxidants; D002243:Carbolines; D002839:Chromans; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C100106:dicarbine