The volume-sensitive outwardly rectifying anion channel (VSOR) is a key component of volume regulation system critical for cell survival in non-isosmotic conditions. The aim of the present study was to test the effects of four tannin extracts with defined compositions on cell volume regulation and VSOR. Preparation I (98% of hydrolysable tannins isolated from leaves of sumac Rhus typhina L.) and Preparation II (100% of hydrolysable tannins isolated from leaves of broadleaf plantain Plantago major L) completely and irreversibly abolished swelling-activated VSOR currents in HCT116 cells. Both preparations profoundly suppressed the volume regulation in thymocytes with half-maximal effects of 40.9 μg/ml and 12.3 μg/ml, respectively. The inhibition was more efficient at lower concentrations but reverted at higher doses due to possible non-specific membrane-permeabilizing activity. Preparations III and IV (54,7% and 54.3% of hydrolysable tannins isolated, respectively, from roots and aboveground parts of Fergana spurge Euphorbia ferganensis B.Fedtch) inhibited VSOR activity in a partially reversible manner and suppressed the volume regulation with substantially higher half-maximal doses of 270 and 278 μg/ml, respectively, with no secondary reversion at higher doses. Hydrolysable tannins represent a novel class of VSOR channel inhibitors with the capacity to suppress the cell volume regulation machinery.
Introduction: The first and most prevailing cells that glycyrrhizin (GL) and glycyrrhetinic acid (GA) encounter are red blood cells (RBCs). However, what follows this event is poorly understood. This study aims to evaluate the effect of GL and its derivatives on the integrity of human RBCs. Methods: The integrity of human RBC was assessed under normal isotonic conditions and following osmotic and nystatin-induced colloid-osmotic stress by measuring the amount of hemoglobin released. The pore size was determined by the osmotic protection method. Results: GL was found to be virtually non-hemolytic. However, removal of the carbohydrate moiety of GL imparted significant RBC lytic activity to the cis-(beta-) but not to the trans-(alpha-) isoform of GA. The hemisuccinate radical at position C3 (carbenoxolone) greatly diminished the hemolytic property of GA. The RBC lysis occurred by colloid-osmotic mechanism due to the formation of hydrophilic pores with the radius of ~2.3 nm. At the sublytic doses, the two stereo-isoforms displayed opposite effects on the osmo-resistivity of human RBC: osmoprotection for alpha-GA and osmotic sensibilization for beta-GA. Similar osmotic sensibilization was also observed for GL and carbenoxolone. The two stereo-isoforms exhibited different but not opposite weakening effects on the resistivity of the RBC to the colloid-osmotic stress induced by nystatin, a pore-former. The weakening effect was found intermediate for GL and absent for carbenoxolone. Conclusion: Upon intestinal digestion and absorption, depending on the structure and dosage, the GL hydrolysis products interact with RBC with both beneficial and detrimental consequences.
Echinococcus granulosus is widespread among cattle, sheep and goats in seasonal pastures. Moreover, this invasion is considered one of the most dangerous zoonoses. The purpose of this work was to compare the indicators of the extensiveness and intensity of invasion of different-aged slaughter livestock (fattening bulls of 1.5–2 years old and 4–7 years old cows) from the herds of four regions of Azerbaijan located in different zones of the country. Based on the results of the expertise of 100 carcasses from each region, it was concluded that the indicators of the extensiveness of the invasion of echinococcosis in cattle were similar and ranged from 21.0–25.0 % with the invasion intensity of 9.36–11.96 specimens of cysts/carcass. To identify larvocysts of Echinococcus granulosus, the carcasses and internal organs of cattle (lungs, liver, kidneys, spleen, heart) were examined. In this case, the extensiveness (EI) and intensity (II) of echinococcosis invasion were established. The indicator of the latter was the number of larvocysts detected in the examined organs of the invaded cattle. Their localization and accounting were determined by counting the echinococcal larvocysts separately in three positions: liver, lungs and others (abdominal cavity, kidneys, spleen and heart). In many cases (73.6 %) the larvocysts were simultaneously found in the liver and lungs. There is a tendency towards an increase in the incidence rate of cattle with age. So, the extensiveness of the invasion of cows was 2.5 times higher than that of the young, and the intensity of invasion was 2.3 times higher. In the future, it is planned to establish the extensiveness and intensity of echinococcosis invasion among flocks of sheep arriving from summer distant mountain pastures in comparison with the number of flocks staying year-round in local near-village pastures.
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