Keyword:Ischemia-reperfusion injury, ischemic postconditioning, hypoxic postconditioning, molecular hydrogen, antioxidants https://mc06.manuscriptcentral.com/cjpp-pubs AbstractGeneration of free radicals through incomplete reduction of oxygen during ischemia/ reperfusion is well-described. On the other hand, molecular hydrogen (H 2 ) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against ischemia/reperfusion (30-min global I/120-min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB). Furthermore, the possibility to potentiate the effect of HpostC by H 2 using oxygenfree KHB saturated with H 2 (H2+HpostC) was tested. HPostC was induced by 4 cycles of 1-min perfusion with oxygen-free KHB intercepted by 1-min perfusion with normal KHB, at the onset of reperfusion. H 2 +HPostC was applied in a similar manner using H 2 enriched oxygen-free KHB. Cardioprotective effects were evaluated on the basis of infarct size (IS, in % of area at risk, AR) reduction, post-I/R recovery of heart function and occurrence of reperfusion arrhythmias. HPostC significantly reduced IS/AR compared to non-conditioned controls. H 2 present in KHB during HPostC further decreased IS/AR compared to the effect of HPostC, attenuated severe arrhythmias, and significantly restored heart function (vs. controls). Cardioprotection by hypoxic postconditioning can be augmented by molecular hydrogen infusion.

Aim To test the hypothesis that valproic acid treatment positively affects brain-derived neurotrophic factor (BDNF) expression and DNA methylation in the hippocampus and brain cortex of rats simultaneously treated with aldosterone. Methods Male Sprague-Dawley rats (N = 40) were treated for two weeks with valproic acid (100 mg/1 kg body weight/day) in drinking water and aldosterone (2 μg/100 g body weight/day) or placebo via subcutaneous osmotic minipumps. Results Treatment with valproic acid did not modify BDNF gene expression in the hippocampus but reduced BDNF mRNA levels in the brain cortex. Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex. BDNF expression negatively correlated with DNA methylation in the hippocampus of valproic acid-treated rats. An unexpected finding was that aldosterone treatment significantly decreased global DNA methylation in the hippocampus. Conclusion The effect of valproic acid on BDNF expression in the brain may depend on the extent of pathological changes present at the time of treatment onset. The observed negative correlation between BDNF expression and DNA methylation in the hippocampus of valproic acid-treated rats encourages further studies.

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