The Influence of Corvitin on the Cholates Content in the Male Rats’ Liver under the Conditions of Chronic Social Stress

The creation of universally effective and safe correctors of biliary secretion disorders is becoming more timely. There is an urgent need for scientists to find drugs that would correct blood cholesterol levels and metabolism in liver effectively and without limiting side effects. The purpose of the study was to investigate the possibility of using corvitin to correct stress-induced biliary disorders of the liver of male rats. Materials and methods. The article looks at recent research dealing with changes in the bile acid composition of outbred male rats’ bile under chronic social stress (social defeat in daily male confrontations, 14 days) when using Corvitin (1 mg/kg, intragastrically, 7 days). Chronic social stress was created by daily agonistic interactions between animals. The state of memory and the level of research activity in the object recognition test (cognitive test) were also studied. The main fractions of conjugated bile acids (taurocholic, taurohenodeoxycholic and taurodeoxycholic, glycocholic, glycochenodeoxycholic and glycodeoxycholic and free ones – cholic, chenodeoxycholic and deoxycholic) were determined by the method of thin layer chromatography of bile. Results and discussion. Chronic social stress leads to a slight increase in the overall activity of the experimental animals, but significantly impairs the processes of recognition and memory. Social stress significantly inhibits the processes that ensure the synthesis, biotransformation and transport of bile acids in the bile. Also, chronic social stress causes changes in bile production, which reduce the solubilization properties of bile and increase the risk of lithogenesis. Conclusion. The use of Corvitin simultaneously with the simulation of experimental social stress normalized the biliary secretory function of the liver, which indicates a high potential for the use of Corvitin as a corrective factor in chronic social stress. Corvitin used by us in the conditions of experimental social stress to some extent corrected the content of bile acids in the liver of male rats, which indicates the ability of this drug to interfere with the metabolism of cholate in liver cells, in the mechanisms of bile acid transport. Correction of stress-induced pathologies of liver bile-secretory function by Corvitin requires further thorough experimental studies

miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

Ketamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.

The effect of Corvitin on the content of bile acids in the liver of rats under conditions of chronic social stress

The article looks at recent research dealing with changes in the bile acid composition of the bile of outbred male rats under chronic social stress (social defeat in daily male confrontations, 14 days) when administered Corvitin (1 mg/kg, intragastrically, 7 days). Chronic social stress was created by daily agonistic interactions between animals. The main fractions of conjugated bile acids – taurocholic, taurohenodeoxycholic and taurodeoxycholic, glycocholic, glycochenodeoxycholic and glycodeoxycholic and free ones – cholic, chenodeoxycholic and deoxycholic were determined by the method of thin layer chromatography of bile. The conjugation index (ratio of the sum of conjugated cholates to the sum of free ones) and hydroxylation (ratio of the sum of trihydroxycholanic bile acids to the sum of dihydroxycholanic ones) of bile acids were calculated. The research showed that in the conditions of experimental social stress, Corvitin enhances the conjugation of bile acids with taurine and glycine, i.e. stimulates detoxification processes in hepatocytes. In the conditions of chronic social stress in male rats, the processes that had provided the flow of glycoconjugates of bile acids from hepatocytes to the bile ducts were further suppressed. The concentrations of glycocholic acid and glycochenodeoxycholic and glycodeoxycholic acids in the bile of male intruders were lower than the control values. But, as seen in the experiment, the use of Corvitin normalized these indicators. The experiment showed that in the conditions of chronic social stress, the content of cholic acid in the bile of intruder rats decreased, and when correcting the pathological condition using Corvitin, it reached the control values. The use of Corvitin simultaneously with the simulation of experimental social stress normalized the biliary secretory function of the liver, indicating the high potential of using Corvitin as a corrective factor in chronic social stress. Correction of stress-induced pathologies of liver bile-secretory function by Corvitin requires further thorough experimental studies.

Elevated cortisol lowers thermal tolerance but results in limited cardiac remodelling in rainbow trout (Oncorhynchus mykiss) experiencing chronic social stress

Juvenile rainbow trout (Oncorhynchus mykiss) held in pairs form dominance hierarchies in which subordinate individuals experience chronic social stress accompanied by lowered thermal tolerance (assessed as the critical thermal maximum, CTmax). Here we tested the hypothesis that chronic elevation of circulating cortisol levels reduces thermal tolerance in subordinate trout. In support of this hypothesis, subordinate trout that recovered from social stress for 48 h, a period sufficient to return cortisol to normal baseline levels, no longer showed reduced CTmax. Further, thermal tolerance was not restored in subordinates treated with cortisol during recovery from social stress. To explore possible mechanisms underlying the effect of chronic stress on CTmax, we also tested the hypothesis that chronic cortisol elevation induces cardiac remodelling in subordinate trout, as previously reported for cortisol-treated rainbow trout. Ventricle mass and cardiac hypertrophy markers were unaffected by social stress. Picrosirius red staining revealed a trend for lower collagen levels in the ventricles of subordinate relative to dominant trout. However, collagen type I transcript and protein levels, and markers of collagen turnover were unaffected. Indicators of cardiac function, including ventricle passive stiffness and intrinsic heart rate (fH), similarly were unaffected. In vivo fH was also similar between subordinate and dominant fish. Nevertheless, in keeping with their lower CTmax, subordinate fish exhibited cardiac arrhythmia at significantly lower temperatures than dominant fish during CTmax trials. Thus, high baseline cortisol levels in subordinate trout result in lowered thermal tolerance, but 5 d of social stress did not greatly affect cardiac structure and function.