Anti-apoptotic effects of 2-pyrrolidone derivatives in cerebral ischemia

INTRODUCTION: Uncontrolled course of apoptosis reactions underlies a wide range of pathological processes, including ischemic events. AIM: To evaluate the anti-apoptotic properties of some racetams in experimental brain ischemia in rats. MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible occlusion of the middle cerebral artery. The test-compounds and the reference drug piracetam were administered per os at a dose of 250 mg/kg. After 72 hours of the ischemic period, the activity of apoptotic systems in the brain tissue was evaluated by determining the concentration of the apoptotic-inducing factor (AIF), caspase-3, ionized calcium, the latent opening time of the mitochondrial transition permeability pore and the zone of brain necrosis. RESULTS: The study showed that the use of the studied compounds contributed to a decrease in the intensity of reactions, both caspase-dependent and caspase-independent apoptosis, which was reflected in a decrease in the concentration of AIF and caspase-3 by 32.4% (p < 0.05); 34.6% (p < 0.05); 31.1% (p < 0.05), and 41.9% (p < 0.05); 39.1% (p < 0.05); 34.5% (p < 0.05) when PirPr, PirAc and PirBut were administered, respectively. Also, the use of the studied substances led to an increase in the latent period of opening the mitochondrial transition permeability pore, a decrease in the concentration of intracellular calcium and the zone of brain necrosis. At the same time, the pharmacological effect of the administration of the compound PirAc exceeded the effect of piracetam and other test substances. CONCLUSIONS: Based on the results obtained, it can be assumed that the studied racetams have neuroprotective action, realized through suppression of the reactions of apoptosis.