Background. Stress is one of the main causes of the development of most diseases. The role of proteolysis in the pathogenesis of post-stress reactions is not sufficiently elucidated. Aim. To investigate the effect of “mild” stress on the state of proteolysis in the oral mucosa (OM). Methods. Rats were subjected to “mild” stress by holding them at −20 °C for 5 minutes. In the OM, in blood serum, liver, kidneys and pancreas, proteolysis activity was determined by the rate of hydrolysis of two substrates: casein and BAEE (benzoyl-arginine ethyl ether). Results. It has been established that OM has a high proteolytic activity, which begins to decrease already 5 hours after stress. In blood serum, on the contrary, the activity of proteolysis (substrate casein) increases after stress. The activity of BAEE-esterase does not change significantly after stress. Conclusion. The level of proteolysis in OM is several times higher than the corresponding indicator for blood serum and rat liver. "Mild" stress causes an increase in the level of proteolysis in the blood serum as early as 5 hours after stress, while the level of proteolysis in the OM after stress tends to decrease. Activation of proteolysis in the blood after stress requires antiprotease actions using protease inhibitors.
Background: Water-sodium homeostasis regulation is a fundamental physiological process that ensures cellular function maintenance, extracellular fluid volume, and arterial pressure. Despite decades of research, the integrated understanding of the dual sodium regulatory system remains incomplete, limiting the development of effective therapeutic approaches for cardiovascular and renal diseases. Objective: To conduct a systematic review and meta-analysis of evidence regarding integrated dual regulation of water-sodium homeostasis, including cellular mechanisms (digitalis-like compounds and Na-K-ATPase) and systemic mechanisms (natriuretic peptides and neurohormonal volume regulation), with assessment of their pathophysiological interactions and clinical implications. Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus databases (1957-2025) according to PRISMA 2020 guidelines. Experimental studies, clinical trials, and observational studies investigating sodium regulation mechanisms at cellular and systemic levels were included. Study quality was assessed using RoB 2.0, ROBINS-I, and Newcastle-Ottawa Scale. Meta-analysis was performed using random-effects model (DerSimonian-Laird). Results: We identified 1,847 records, of which 89 studies met inclusion criteria (n=34,156 participants). Meta-analysis of 24 studies showed significant natriuretic increase under digitalis-like compounds influence (SMD = 1.67, 95% CI: 1.52-1.82, p<0.001, I²=68%). Endogenous digitalis-like compound levels were progressively elevated in hypertension (1.87±0.64 vs 0.52±0.18 nmol/L in healthy individuals, p<0.001), heart failure (2.34±0.89 nmol/L), and chronic kidney disease (2.78±1.12 nmol/L). Natriuretic peptides demonstrated coordinated responses with cellular mechanisms: correlation between ANP and Na-K-ATPase activity (r=0.58, p<0.01), BNP and endogenous ouabain levels (r=0.42, p<0.05). Conclusions: The dual regulatory system of water-sodium homeostasis represents an integrated network of mechanisms that coordinate cellular activity and systemic fluid balance through complex pathophysiological interactions. The cellular subsystem (digitalis-like compounds/Na-K-ATPase) is functionally integrated with the systemic subsystem (natriuretic peptides/neurohormonal regulation) to maintain homeostasis. Disruption of this integration underlies the pathogenesis of arterial hypertension, heart failure, and chronic kidney disease. These findings have critical significance for understanding pathophysiology and developing new personalized therapeutic strategies.
Background. Stress is one of the important causes of the development of pathological processes in the body. The salivary glands play a certain role in the pathogenesis of post-stress pathological reactions Aim. To determine the state of the submandibular gland of rats after "mild" stress (−20 °C, 5 minutes) by such indicators as proteolysis, kallikrein-kinin system, and oxidation. Methods. The state of proteolysis was assessed by the rate of casein hydrolysis (pH 7,6) according to the Kunitz method, the state of the kallikrein-kinin system was determined by the rate of BAEE (benzoyl-arginine ethyl ether) hydrolysis, and the oxidation activity was determined by the rate of ascorbic acid oxidation. Results. It has been established that in rats after stress, the level of proteolysis increases (significantly after 24 hours) and the level of oxidation increases very strongly (almost 6 times). The activity of BAEE esterase does not significantly respond to “mild” stress. Conclusion. The submandibular gland is sensitive to "mild" stress, increasing the activity of oxidation and proteolysis processes.
Background. It is known that stress negatively affects the liver. Under the influence of stress factors, oxidative stress occurs in the liver, which is the main pathogenetic mechanism of hepatitis development. In the process of post-stress reactions, other pathogenetic processes are also activated, due to the activation of hydrolytic processes, increased permeability of histo-hematic and intestinal barriers. Aim. To investigate the effect of stress on the condition of the liver. Methods. Rats were stressed by holding the animals at −20 °C for 5 minutes (“mild” stress). 5 and 24 hours after stress, proteolysis activity (substrate casein, pH 7,6; substrate albumin, pH 5,5) was determined in the liver by the Kunitz method, BAEE esterase activity by the spectrophotometric method, and oxidative status by the rate of ascorbic acid oxidation. Results. After 24 hours, a decrease in proteolysis activity is observed (substrate casein, pH 7,6) and after 5 hours the level of peroxidation decreases. Albumin proteolysis activity (pH 5,5) does not change. There is a tendency to increase BAEE-esterase activity. Conclusion. A decrease in the level of proteolysis and oxidation may indicate a positive effect of “mild” stress on the condition of the liver.
Background: Water is the fundamental basis of life and an absolute prerequisite for the existence of proteins and all biological structures. During evolution, an extraordinarily complex multilevel system of water homeostasis has developed in the human body, with diverse executive mechanisms at each level of biological organization. Objective: Comprehensive analysis of molecular, cellular, and systemic mechanisms of water-protein interactions in the context of human physiology, with particular emphasis on the role of urea as a regulator of protein hydration, the function of plasma proteins in maintaining oncotic pressure, and the pathophysiology of hepatic hypoproteinemia. Methods: Narrative literature review with systematic search in PubMed, Scopus, and Web of Science databases for the period 1980-2025. Over 80 scientific sources were analyzed, including original research, systematic reviews, and clinical studies. Special attention was paid to the works of Professor A.I. Gozhenko and co-authors on water-salt homeostasis. Results: Protein hydration layers consist of several zones with varying degrees of ordering (first layer 0.25-0.35 nm, second layer 0.35-0.6 nm), with the rotational relaxation time of water molecules in the first layer being 2-5 times longer than in bulk water. Urea demonstrates a concentration-dependent dichotomy: at physiological concentrations (5-500 mM) it functions as a compatible osmolyte, while at high concentrations (6-8 M) it acts as a denaturant. Albumin, comprising 60% of plasma protein mass, generates 75-80% of oncotic pressure (25-28 mmHg) due to the Donnan effect and nonlinear dependence π = RT·C·(1+kC). Aquaporins transport up to 3×10⁹ water molecules/s, while Na⁺/K⁺-ATPase creates ionic gradients by exporting 3 Na⁺ and importing 2 K⁺ per ATP molecule. Vasopressin, via V2 receptors, activates the cAMP-PKA cascade, leading to AQP2 phosphorylation at Ser256 and its translocation to the apical membrane. Hepatic hypoalbuminemia (<25-30 g/L) disrupts Starling balance, activating RAAS and ADH, which paradoxically exacerbates edema. Conclusions: Water homeostasis is maintained through hierarchical integration of molecular (protein hydration, urea role), cellular (aquaporins, Na⁺/K⁺-ATPase), tissue (Starling balance, oncotic pressure), and systemic (hypothalamic-pituitary-renal axis) mechanisms. Disruption at any level leads to a cascade of pathological changes, emphasizing the need for an integrative approach to the diagnosis and treatment of water balance disorders.
