Investigation of the protective effect of hesperidin and its combined use with amino acids on the permeability of cerebral vessels against the background of ir-radiation

Introduction. Epidemiological and clinical studies indicate the importance of flavonoid consumption for the prevention of cardiovascular diseases in particular. It is known that a diet enriched with flavonoids significantly increases the resistance of red blood cells to oxidative stress. Despite the great interest in flavonoids as potential means of protection against many human diseases, the real contribution of these compounds to maintaining health and the mechanisms by which they act are still unclear. According to available studies, the flavonone hesperidin is an antioxidant, capable of normalizing permeability and strengthening the walls of capillaries, protecting them from the damaging effects of free radicals and peroxide products. In this regard, it was of interest to directly evaluate the effect of both hesperidin itself and its artificial mixtures with amino acids on the permeability of the capillary wall of the brain.

The purpose of the study – study of the effect of the flavonoid hesperidin and its combinations with amino acids (glycine and lysine) on the permeability of cerebral vessels against the background of irradiation.

Material and methods. The objects of the study were the flavonoid hesperidin (isolated from citrus peel) and individual amino acids: lysine (HiMedia Laboratories, India), glycine (Sigma-Aldrich, Merck KGaA, Germany). The effect of hesperidin and the studied mixtures of hesperidin with amino acids mixture I – hesperidin-lysine (1:1) and mixture II – hesperidin-lysine-glycine (1:1:1) it was studied during the height of acute radiation sickness on the transcapillary exchange of the brain of white nonlinear sexually mature white rats. The studied compounds were administered in the form of an aqueous suspension to unirradiated animals and on the background of irradiation. Irradiation was carried out by the method of short-term general radiation exposure on a standard Agat-C therapeutic apparatus (dose 2 Gy, power 0.0171 Gy/sec, RIP 75 mm, area 20×20, Co⁶⁰). Capillary permeability (transcapillary metabolism) was determined by comparing hematocrit and protein content in arterial and venous blood.

Results. Experimental studies confirm the activity of hesperidin and its combination with amino acids for a normalizing effect on the permeability of cerebral vessels. In unirradiated rats, the fluid output from the blood into the tissue was approximately 4.30 ± 0.03 ml for every 100 ml of blood, and the permeability of brain capillaries to protein averaged –2.5 ± 0.27% of the protein lost by tissues for every 100 ml of blood. On the 14th day after radiation exposure (the period of the height of acute radiation sickness in animals of the control group, the fluid output from the capillary bed was 5.9±0.21 ml/%, which was significantly higher than in non-irradiated animals by 37% (p<0.05). The loss of protein by tissues in these animals also significantly increased by more than 5 times compared with the indicators of non-irradiated rats. In rats treated with hesperidin and mixture II before irradiation, a significant decrease was observed after irradiation compared with the control of the permeability of brain capillaries for protein by 72% and 69%, respectively (p<0.05), i.e. about equally. At the same time, index characterizing the release of fluid from the blood into the tissue in these rats did not significantly change in comparison with control animals. At the same time, in rats injected with mixture I, a more pronounced significant decrease in the permeability of brain capillaries to protein by 80% was observed under the same conditions compared with the control, as well as a significant decrease in the release of fluid from the blood into the tissue by 17%.

Conclusions. Hesperidin and its mixtures with amino acids have the ability to strengthen capillary walls against the background of irradiation, leading to an increase in their permeability. It has been established that adding the amino acid lysine to hesperidin increases the effectiveness of its protective action, but not together with glycine. In this regard, the combination of hesperidin with lysine can be recommended for further studies on their use for the prevention of vascular pathology caused by irradiation.