Liashevych A. The effects of corvitin on the liver's bile secretion function under chronic social stress and hypercholesterolemia

The dissertation is devoted to the study of the effect of social stress and hypercholesterolemia on the bile secretion function of the liver when using corvetone. Carrying out the chronic social stress can change mental state of a person and disturb the different system's functioning as well. Pathological alteration of central regulatory mechanisms is the underlying cause of stress-induced functional diseases. Since liver functioning itself undergoes difficult neurohumoral regulation any stress-induced disturbance in neural and humoral regulation mechanisms can produce direct or mediated action on its functioning. It was revealed that chronic social stress during two weeks reliably reduced memory state and level of recognition of a new object in Novel Object Recognition behavioral test. Animals exposed to chronic stress also shows advanced investigative behavior level which can be explained by some total activation in rats in the issue of stressing procedure. Thus chronic social stress leads to certain increase of the rats activation level but reliably suppresses the recognition and memorizing processes. Chromatographic analysis of bile's organic composition revealed that in rats subjected to chronic social stress bile acids compound considerably changed compare to control animals. Regarding our data we can suggest that chronic social stress provokes depression of the classical way of bile acids synthesis and inhibition of a secondary litocholic acid biotransformation. Bile acids changed by stress-induced regulatory factors can later be regulators themselves and modulate physiological and pathological consequences of the stress. We suggest that disturbance of a bile's synthesis, transformation and transport in hepatocytes plays a significant role in the metabolic disease's pathogenesis. Obtained data shows that chronic social stress caused specific metabolite processes in male-rats liver which leads to changes in the bile's lipid content as long as it depressed the processes providing bile's steroid components input in the primary bile ducts. By calculating of a cholat-cholesterol ratio it revealed that bile's lytogenous capacities (rise of the probability of cholesterol gallstone formation) appears in a month after chronic social stress experience. In the condition of doxicyclin-induced hypercholesterolemia bile secretion apparatus unable to realize its cholesterol-elimination function. It was shown that in the rats exposed to chronic social stress, the composition of the cholates of bile significantly changes compared with the animals of the control group. It was found that under conditions of chronic social stress in the liver of male rats there occur metabolic processes that lead to a change in the lipid composition of bile animals, in hepatocytes of male rats, the processes suppressing the inflow into the primary bile ducts of the steroid lipid components of the bile are predominantly suppressed. According to the calculations of the cholato-cholesterol ratio, it was found that the lithogenic properties of bile manifest within a month after the animals were subjected to social stress. It was shown that the use of corveton in rats exposed to the previous doxycycline loading, contributes to the normalization of the processes of conjugation of free cholates in hepatocytes and their introduction into bile, and also leads to the normalization of the content of phospholipids in their bile. The results indicate that social stress significantly inhibits the processes that ensure the synthesis, biotransformation and transport of bile acids into bile, resulting in the increased liver secretion of stressed rats of free dihydroxycholate xenodeoxycholic and deoxycholic acids and a significant amount of secondary monohydroxycholan lithocholar and taurolitohole acids that are absent in the liver secretion of animals in the control group. Social stress disturbs the processes of cholesterol metabolism in the liver, causing a decrease in the concentration of free cholesterol in the bile and increasing its etherification in hepatocytes. The use of corvetane in conditions of experimental social stress stimulates detoxification processes in hepatocytes; leads to a decrease in the content of free cholesterol and an increase in the number of its ethers in bile.