Pharmacological modulation of Heat Shock Protein 70 (HSP70) - dependent mechanisms of endogenous neuroprotection in conditions of prenatal chronic alcoholism by Cerebrocurin and Tiocetam -

Abstract

Objective: One of the primary reactions of the genome in response to stress is different genesis induction of heat shock proteins – HSP. The purpose of this study was to investigate the concentration of heat shock protein (HSP70) and hypoxia-inducible factor (HIF-1) in the brain of rats undergoing chronic prenatal alcoholism in different periods of ischemia and define the role of these proteins in the implementation of neuroprotective effect of Cerebrocurin and Tiocetam. Methods: Experiments were carried out on female rats weighing 150-180 g. All animals were on standard food ration of vivarium, with natural alteration of day and night. Rats were recieved from nursery of «Institute of Pharmacology and Toxicology, Academy of Medical Sciences of Ukraine». All experimental procedures and operative interventions were done in accordance with WMA Statement on Animal Use in Biomedical Research. Rats from the 5th to the 20th day of gestation received ethanol in a dose of 6-8 g/kg/day, control rats – isocalorific sucrose solution. Offspring of alcoholized rats immediately after birth during 25 days were injected intraperitoneally Tiocetam (125 mg/kg), Piracetam (125 mg/kg) and Cerebrocurin (0.06 mg/kg), control rats received saline solution. There were 20 infants in each group. Biochemical studies carried out on brain on 26 days of the experiment, for this purpose the animals were decapitated under anesthesia using Thiopental (30 mg/kg, intraperitoneally). Concentration in the brain tissue and HIF proteins and HSP proteins were determined by Western blot analysis. Results: Study of concentration in brain tissue HIF proteins and HSP-proteins showed that after undergoing prenatal chronic alcoholism there was an observed decrease in concentration of HSP, so HIF-proteins. Course treatment by Cerebrocurin and Tiocetam resulted in statistically significant increased content of HIF and HSP proteins in the brain in comparison with a group of untreated animals. Neuroprotective activity of Cerebrocurin and Tiocetam was observed in reduction of neurological deficit, as evidenced by the statistically significant decrease in the average score on a scale of C.P. McGrow. Cerebrocurin and Tiocetam directly or indirectly can modulate the expression of early response c-fos genes and thus the “run” software adaptation protein synthesis (including HSP and HIF) in neurons with acute cerebral ischemia. Conclusion: Implementation of the neuroprotective effect of Cerebrocurin and Tiocetam revealed apparently their ability to increase the concentration in the brain tissues of HSP-protein.