Vol 60, No 5 (2024)

UDP-glycosyltransferases (UGTs) are enzymes from a complex superfamily of glycosyltransferases. UGTs catalyze glycosylation reactions, i.e. the covalent addition of sugar from a cofactor (UDP-glycoside) to the corresponding functional group of a lipophilic substrate. These enzymes play a crucial role in cellular homeostasis of many groups of organisms (mammals, arthropods, plants, etc.). UGTs are the main enzymes of phase II detoxification of xenobiotics of various origins (metals, natural compounds, drugs, industrial pollutants, pesticides, etc.). The human UGTs arouse interest due to their role in drug metabolism and involvement in the development of drug resistance in cancer cells. UDP-glycosyltransferases of invertebrates (especially insects) attract the attention of researchers because of their involvement in the development of pesticide resistance. However, the exact role of individual UGT families and subfamilies in xenobiotic biotransformation remains unclear, highlighting the importance of further study of these enzymes. This review aims to provide an understanding of the diversity of UDP-glycosyltransferases in vertebrates and invertebrates (arthropods) and some details of the interaction of these enzymes with xenobiotics. The section on general information briefly describes the structure and localization of the enzymes of the superfamily UGTs, the enzymatic reaction and the mechanism of catalysis using UDP-glucuronosyltransferase as an example. In addition, this review presents the data on the impact of different xenobiotics (industrial pollutants, metals, pesticides, drugs and natural compounds) on the enzymatic activity of UGTs and the level of UGT gene expressions in vertebrates and invertebrates (arthropods). The diversity of UGT enzymes and their substrates reflects the wide possibilities of the animal organism to protect themself from xenobiotics.

The osmotic fragility of erythrocytes serves as a crucial parameter indicating the cells' ability to endure variations in the osmotic environment. Disorders in this attribute are often correlated with a spectrum of pathologies, encompassing hemolytic anemias, malignant tumors, and cardiovascular dysfunctions. Notably, osmotic fragility exhibits variability across different animal species and closely intertwines with their respective ecosystems. A methodology for assessing osmotic fragility has been devised utilizing a laser particle analyzer, facilitating the real-time monitoring of cell concentration changes under controlled temperature conditions. The species examined include Homo sapiens, Rattus norvegicus domestica, Coturnix japonica domestica, Rana ridibunda, Carassius carassius, and Lampetra fluviatilis. The methodology is presented in two variants: (1) manual water additions and (2) automated medium dilution. Key parameters characterizing osmotic fragility include H₅₀ (the osmolality causing lysis in half of the susceptible cells), H₉₀ (lysis in 90% of the cells), and W (heterogeneity in lysis fragility within the cell population). The findings obtained through the developed method did not show statistically significant deviations from the results obtained using spectrophotometry and flow cytometry concerning parameters such as H₅₀ and W. Moreover, no noteworthy disparities were observed between the outcomes of the automatic and manual methodologies. Erythrocytes of aquatic and semi-aquatic animals exhibit significantly higher resistance to hypotonic lysis. Among all species examined, amphibian (Rana ridibunda) and lamprey (Lampetra fluviatilis) erythrocytes demonstrated the lowest osmotic fragility. The most pronounced variability in resistance levels was detected among amphibians, with differences nearly doubling in comparison to other taxa examined. While mammalian erythrocytes (including those of humans and rats) exhibited similar fragility levels, they displayed less uniformity in their resistance profiles. Bird erythrocytes, on the other hand, demonstrated a half-lysis occurrence at higher osmolality levels compared to mammalian erythrocytes. Nonetheless, bird erythrocytes (Coturnix japonica domestica) lysed over a considerably wider osmotic range and contained a subset of cells resilient to hypotonic lysis. These findings indicate that erythrocytes of lower vertebrates possess lower osmotic fragility compared to those of higher vertebrates, a phenomenon likely attributable to embryonic characteristics, ecto-/endothermy, and habitat considerations.

The temperature coefficients Q10 of heart rate (Q10_HR) or oxygen consumption (Q10_Ox) were analyzed during the arises from torpor of long-tailed ground squirrels Urocitellus undulatus, as well as during the rewarming of precooled adult rats and rat pups. The Q10_Ox value was calculated using a standard equation, whereas for calculating Q10_HR, the equation was empirically modified to track changes in this parameter over a wide range of body temperatures (T_b). It was found that during the initial period of rewarming from torpor, at T_h ≤ 10 ℃, ground squirrels experienced a sharp increase in the temperature coefficients up to Q10_HR = 40 – 50 and Q10_Ox = 6 – 7. Even higher values of Q10_HR > 100 were found at the beginning of rewarming of rat pups, although they had a low level of Q10_Ox = 1.2. Adult rats could not withstand cooling below 16 ℃ and demonstrated moderate variability of both Q10_HR = 2.0 – 4.0 and Q10_Ox = 2.0 – 2.2. During the restoration of normal T_b, the Q10_HR in all animals approached the level ~2.0 predicted by the Van't Hoff-Arrhenius rule for chemical reactions in both living and inanimate nature. We assume that high values of Q10_HR and Q10_Ox, detected in the early period of ground squirrel’s arousal from hibernation, may reveal the functioning of adaptive processes aimed at accelerating body warming. Resistance to cooling and high Q10_HR coefficient in the rat pups may indicate rudimentary adaptability to hibernation in the juvenile period of rats, as representatives of the order Rodentia, which also includes natural hibernators such as ground squirrels.

Hyperbaric oxygen (HBO₂) breathing induces generalized tonic and clonic seizures through poorly understood mechanisms. The purpose of the research was to evaluate the mechanisms of involvement of monoamine oxidase (MAO) in the development of hyperbaric oxygen convulsions. In rats placed in a pressure chamber under an oxygen pressure of 5 ATA, convulsive reactions were analyzed after the administration of pyrazidol, a MAO-A inhibitor, and pargyline, a MAO-B inhibitor. Studies have shown a decrease in the activity of MAO isoforms in HBO₂ as well as a delay in the development of seizures in animals with inhibition of MAO-A and MAO-B. The level of GABA in the brain decreased with HBO₂, and inhibition of MAO-B with pargyline prevented the decrease in the inhibitory transmitter. The results indicate that MAO isoforms play an important role in regulating epileptogenesis in extreme hyperoxia. Hyperbaric oxygen, inhibiting the catalytic activity of MAO by transforming its molecular structure, leads to disruption of the regulation of the exchange of monoamine neurotransmitters and a decrease in the level of GABA in the brain, which together leads to an imbalance of excitation/inhibition processes in the central nervous system, which is the basis for the development of oxygen epilepsy.

The participation of the glutamatergic neurotransmitter system in the pathogenesis of audiogenic seizures (AS) and post-ictal catalepsy (PIC) in Krushinsky-Molodkina rats was analyzed. Effects of D-serine and disocilpine administration was investigated. In intact KM rats, the intensity of AS correlates with the duration of PIC. The administration of D-serine (acute administration, doses of 200, 400 and 600 mg / kg, as well as after chronic administration – 5 days of 300 mg / kg, n = 34) had no significant effect on AS and PIC. Disocilpine (MK-801, a non-competitive NMDA antagonist) was administered in an acute experiment at doses of 0.1, 0.2 and 0.4 mg/kg (n = 41). MK-801 dose-dependently reduced the intensity of AS and caused a "two-wave pattern" of seizures in the most of animals, and removed PIC at a lower dose than AS seizures. PIC was completely eliminated already at a dose of 0.2 mg/kg, while the clonic component of AS still persisted. Thus, it was possible to show the "dissociation" of AS and PIC. It is assumed that although dopaminergic control is involved in the mechanisms of PIC development, glutamatergic neurotransmission is also taking part in the PIC expression.

The dependence of prolactin gene (Prl1) expression on sex in the brain and its receptors (PrlRa and PrlRb) in the brain, kidneys, gills, and intestine of the three-spined stickleback (Gasterosteus aculeatus L.) was studied in the context of freshwater adaptation. Males and females of the marine morph were adapted to freshwater for 72 hours, and the expression levels of Prl1 in the brain and PrlRa and PrlRb in the examined organs were assessed using RT-PCR. In seawater, no sex differences in Prl1 gene expression in the brain were observed; however, after freshwater adaptation, significant sex differences were detected due to increased Prl1 expression in females. In the brains of females, PrlRa gene expression was significantly lower in seawater compared to males but increased significantly after freshwater adaptation, eliminating sex differences. PrlRb gene expression in the brain increased significantly in females following freshwater adaptation. In the kidneys, no sex differences in PrlRa gene expression were found in either seawater or freshwater, although expression significantly decreased after freshwater adaptation in both sexes. PrlRb gene expression in the kidneys showed no sex differences in seawater but did so under freshwater conditions due to a significant increase in females and a decrease in males. In the gills, the expression of PrlRa and PrlRb genes was independent of both sex and salinity. In the intestine, neither sex nor salinity influenced the expression of the PrlRa gene. PrlRb gene expression in the intestine showed no sex differences and decreased in both sexes after transitioning to freshwater. It is concluded that the osmoregulatory function of prolactin's dependence on sex is manifested in the sex differences in the expression of the prolactin gene itself and in the sensitization of the brain and osmoregulatory organs to it during freshwater adaptation.