Volume 60, Nº 3 (2024)

Leptin, secreted by adipose tissue, indirectly stimulates the activity of GnRH-producing neurons of the hypothalamus and thus regulates the functional activity of the hypothalamic-pituitary-testicular (HPT) axis. As is known, the obesity is accompanied by systemic hyperleptinemia and impaired leptin transport in the central nervous system, which limits the use of full-length leptin as a drug. It was previously shown that intranasally administered leptin fragment MA-[D-Leu4]-OB3 (LF) enhances the steroidogenic effect of human chorionic gonadotropin (hCG) in rats fed a standard diet. An even more urgent task is to assess its effect on testicular steroidogenesis in conditions of obesity, which reduces reproductive functions in men. The aim of the work was to study the ability of LF (200 μg/kg, intranasally, 3 days) to modulate the effect of hCG (10 IU/rat, subcutaneously, once) on testicular steroidogenesis in rats with obesity induced by a high-fat/high-carbohydrate diet (HFHCD), and also to evaluate influence of the GnRH receptor antagonist cetrorelix (ANT, 75 µg/kg, subcutaneously, 3 days) on the effects of LF. Male Wistar rats were used for the study and received HFHCD for 20 weeks. In obese rats, the level of the luteinizing hormone (LH) receptor in the testes was reduced and the expression of the Cyp11a1 gene, encoding the steroidogenic enzyme cytochrome P450scc, was compensatory increased. LF administration enhanced the effect of hCG on the testosterone level in the blood and the expression of the Star gene, encoding the cholesterol transport protein StAR, which indicates the ability of LF to positively modulate the activity of the HPT axis in obesity. Co-administration of ANT and LF, on the contrary, reduced the stimulating effect of hCG on testosterone levels and Star gene expression, which may be due to the testicular effects of LF. Our data indicate the ability of LF to influence various components of the male gonadal axis under conditions of diet-induced obesity.

Mate choice is the very important part of sexual selection. It is known that free mate choice is to provide the most viable offspring are born. Researches on different animal species found that viability from introduction to sexual maturity is significantly higher in individuals born in crossbreeding in accordance with free behavioral mate choice, compared to that in crossbreeding against the mate choice. Making the choice, the female may rely on visual, vocal or olfactory signals of male. Most of experiments evaluating sexual choice allowing interactions with the animal, making it impossible to determine the specific contribution of each separate signal. Odor play a crucial role in intraspecific communication in rodents. Individuals are able to recognize sex, reproductive status, genotype, and diet and health condition conspecifics by odor. However, very few articles unite olfactory signals from the male to information about his paternal effects. In our research, we mated a male with two females. The number of live embryos, their weight and the weight of fetal placentas evaluated reproductive success of males. Naive females in olfactory tests then evaluated the volatile urine fraction of the males. Male urine samples were also analyzed using chromatography-mass spectrometry analysis. In result, the naive BALB/c females prefer males with low number of fetus in the litter compared to males with high number of fetus in the litter. Instrumental method of analysis approved the opportunity to differentiate between the groups of males. Other pregnancy parameters did not affect naive females’ preference for male urine samples.

Doxorubicin (DOX) is a potent chemotherapeutic drug, but its clinical use is hindered by significant side effects on vital organs like the heart, kidneys, lungs, liver, and intestines. Currently, there is a lack of effective drugs that can provide simultaneous cardioprotection and organ protection during chemotherapy. Nicotinamide riboside (NR) holds promise as a pharmacological agent capable of offering comprehensive protection against the systemic toxicity caused by DOX. This study aimed to comprehensively evaluate the morphological characteristics of vital organs (heart, lungs, liver, kidneys) in Wistar rats with chronic doxorubicin-induced cardiomyopathy using various intravenous administration modes of NR as a protective agent. Sixty male SPF Wistar rats weighing 283 ± 22 g were divided into four groups: intact, control (DOX administered intraperitoneally), combined mode (the simultaneous use of DOX and NR) and preventive mode (the preliminary use of NR to realize the cumulative effect in cells, and its further joint use together with DOX) intravenous NR administration. Animal observation spanned two months after drug administration, followed by the collection of hearts, lungs, liver, and kidneys for morphological analysis. Echocardiographic assessment confirmed DOX cardiotoxicity. The study revealed that the hearts, kidneys and lungs exhibited more pronounced toxic effects of DOX compared to the liver. Both NR administration modes demonstrated protective effects, with the preventive regime showing the greatest efficacy in safeguarding vital organs.

Microglia activation by proinflammatory stimuli, including lipopolysaccharide (LPS), is considered among the risk factors for neurodegeneration, but the LPS treatment may also have a neuroprotective effect, which leads to further analysis of the relationship between microglial activation and regulators of cell death. In the present work, a comparative study was carried out on proteins expression of marker for activated microglia Iba-1 and the apoptotic executor protease caspase-3 in the brainstem and prefrontal cortex of rats injected intraperitoneally with endotoxin at different doses and schedules. One day after LPS at a dose of 0.5 mg/kg, single, the Iba-1 and caspase-3 expression in both structures did not differ from control values. Endotoxin administration fourfold at the same dose over 7 days (once every 2 days) led one day after the last injection to a significant increase in the Iba-1 level in the brainstem, which was accompanied by a significant decrease in the expression of caspase-3. The same effects in this structure were observed 7 days after a single injection of LPS at a higher dose of 5 mg/kg. In a 7-day experiment, in contrast to the brainstem, no changes in caspase-3 expression were found in the frontal cortex, and an increase in Iba-1 expression was observed only after a single injection of LPS at a high dose. The detected decrease of caspase-3 level in the brain stem under neuroinflammatory conditions may reflect the development of neuroprotective processes, especially important for the structure responsible for such key body functions as respiration, blood pressure and heartbeat.

To treat the hyperadrenergic form of postural orthostatic tachycardia syndrome, the β_1,2-adrenergic receptor blocker propranolol, the β₁-blocker bisoprolol and the central agonist of inhibitory presynaptic α₂-adrenergic receptors, methyldopa, are used in clinical practice. There is no data in the literature concerning the effects of these drugs on venae cavae flows during postural tests. In acute experiments on anesthetized rabbits, we studied changes of cranial and caudal venae cavae flows during orthostatic (head up tilt by 25°) and antiorthostatic (head down tilt by −25°) tests for 20 s after preliminary pretreatment with propranolol, bisoprolol and methyldopa. Before administration of these drugs, in response to orthostasis at 4 and 20 s, a decrease of the cranial and caudal venae cavae flows was noted. During antiorthostasis, caudal venae cavae flow increased for 4 s, and by 20 s it decreased to the initial value; cranial venae cavae flow decreased by 4 s, and by 20 s it was greater than the initial one. After propranolol pretreatment, caudal venae cavae flow decreased to a greater extent compared with intravenous administration of bisoprolol and methyldopa. After methyldopa administration during orthostasis, by 20 s, the cranial venae cavae flow decreased more pronouncedly than in the caudal venae, while after propranolol and bisoprolol pretreatment under conditions of orthostasis, both cranial and caudal venae cavae flows decreased approximately to the same extent. During antiorthostasis by 20 s after pretreatment with propranolol caudal venae cavae flow increased more than cranial venae cavae flow. In case of pretreatment with bisoprolol and methyldopa, in response to antiorthostasis, cranial venae cavae flow increased not only to a greater extent than caudal venae cavae flow, but also more pronouncedly compared with its increase in rabbits initially. Thus, we concluded, that in case of postural loads after pretreatment with indicated above drugs, there are differences in the mechanisms of blood flows redistribution in the basins of the cranial and caudal venae cavae.