Introduction

Prolonged exposure to unacceptable levels of environmental factors on vessels leads to functional deviations that can develop into pre-morbid and pathological conditions. Studying their impact is an urgent task for addressing issues related to the health and work capacity of the crew [1]. It is known that workers in the water transport sector are exposed to a wide range of occupational hazards, including noise, vibration, electromagnetic fields, rolling, frequent changes in time zones and climatic conditions, etc. [2].

Among the biochemical indicators, two functional groups can be distinguished: reference (glucose, cholesterol, urea, creatinine, total protein, albumin) and dynamic (AST, ALT, ALP, GGT, LDH, HBD, and CPK) parameters. Reference indicators are metabolic substances by their biochemical nature, while dynamic indicators are enzymes.

Object and Methods of Research

To assess the impact of prolonged navigation (4-5 months) on metabolic processes, a comparative analysis of biochemical parameters was conducted on 98 men—crew members (average age 46.08 ± 13.44 years)—working in water transport in the Republic of Sakha (Yakutia).

Blood samples for examination were taken from the antecubital vein in the morning on an empty stomach, followed by centrifugation for 15 minutes at 3000 rpm. The activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK), creatine kinase-MB (CK-MB), gamma-glutamyl transferase (GGT), aspartate and alanine aminotransferases (AST, ALT), as well as levels of glucose, total protein, albumin, triglycerides (TG), urea, creatinine, uric acid (UA), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were determined using an enzymatic method on an automatic biochemical analyzer "Labio-200" (China) with reagents from "Analiticon" (Germany). Low-density and very low-density lipoproteins (LDL, VLDL) were calculated using the following formulas: LDL = TC – VLDL – HDL, where LDL is low-density lipoproteins, TC is total cholesterol, and HDL is high-density lipoproteins; VLDL = TG / 2.2, where VLDL is very low-density lipoprotein cholesterol, and TG is triglycerides. The atherogenic index (AI) was calculated using the formula: AI = (TC – HDL) / HDL, where AI is the atherogenic index, TC is total cholesterol, and HDL is high-density lipoprotein cholesterol. The De Ritis coefficient (DRC) was calculated using the formula: DRC = AST / ALT, where DRC is the De Ritis coefficient, AST is aspartate aminotransferase, and ALT is alanine aminotransferase. Laboratory studies were conducted under conditions of constant internal and external quality control. For statistical processing of the obtained data, the licensed SPSS version 22.0 software (StatSoft Inc, USA) was used. The equality of sample means of two numerical sets was tested using the non-parametric Mann-Whitney U test for independent samples. In all cases, p < 0.05 was considered statistically significant.

Results of the Study

Descriptive analysis revealed that the median glucose level after navigation was 5.67 mmol/L, which exceeds the upper limit of the norm (≥ 5.5 mmol/L). All other medians of biochemical parameters were within the normal range and did not exceed the upper limits of normal (see table).

Comparative analysis established statistically significant differences in 9 biochemical parameters. After the voyage, all identified differences, except for LDH and the De Ritis coefficient (AST/ALT), were characterized by increased values compared to the data before navigation. The plasma glucose level is one of the most important homeostatic constants of the body.

Table  1 Dynamics of Changes in Biochemical Parameters in Crew Members

The significant increase in glucose levels after the voyage is likely associated with the enhancement of gluconeogenesis processes, as indicated by the normal levels of OHS [3]. According to Panin L.E., survival under conditions of prolonged psycho-emotional stress is impossible without the involvement of not only steroid hormones but also pancreatic hormones in the regulatory process. An imbalance in the levels of these hormones leads to the development of "stress diabetes" and a shift from carbohydrate metabolism to lipid metabolism [4]. The disturbances in carbohydrate metabolism are based on disruptions in protein metabolism, which is responsible for the synthesis of regulatory hormones [5]. According to the authors (Bichkaeva F.A., Vlasova O.S., Shengof B.A., et al.), changes in glucose levels and its metabolites towards an increase among residents of the Arctic region are associated with a metabolic shift towards disadaptation [6].

Creatinine has high biological activity and maintains a strict physiological constant (60-80 µmol/L). In our study, the level of creatinine in crew members after navigation was elevated (p=0.000) compared to baseline data. It is known that creatinine is a conserved form of creatine, and creatine, in turn, is a substrate for phosphate extraction from mitochondria with the involvement of CK (creatine kinase). The increase in creatinine by the end of the voyage may be associated with the activation of energy recovery during the depletion of energy potential [5].

To date, many authors consider the level of uric acid (UA) in serum as a risk factor for the development of cardiovascular diseases and metabolic disorders [7]. The level of UA in the blood is a variable parameter and depends on various factors such as age, sex, race, dietary habits, and others. UA is closely related to impaired metabolic indicators, kidney function, and smoking [8]. According to the authors [9], an increase in UA levels independently protects against the development of metabolic syndrome (MS), indicating a possible role of UA as an antioxidant in the pathogenesis of MS. In our study, the mechanism of the significant increase in UA after navigation (p=0.000) is related to its protective antioxidant function.

If we consider the dynamic biochemical indicators as enzymes, the analysis results revealed that crew members showed statistically significant increases in CK (creatine kinase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase), and ALT (alanine aminotransferase) after navigation, with the exception of LDH (lactate dehydrogenase) (Table 8).

The level of LDH (lactate dehydrogenase) in serum significantly decreases after the voyage (p=0.000). LDH provides the oxidative-reductive potential of the body, participating in maintaining a stable pH level and serving as a conditionally standard indicator of the organism. It is known that carbohydrate metabolism determines the primary energy homeostasis of the body. At the crossroads of carbohydrate metabolism pathways, LDH is involved not only in regulating finely balanced catabolism and anabolism, anaerobic and aerobic glycolysis, but also in gene expression [10]. It is known that under any overloads of the body, including psychological stress, energy (caloric) expenditure increases to overcome adverse circumstances [11]. According to the authors, the reduction of the energy-producing enzyme LDH in older men may be one of the mechanisms for depleting the energy resources of leukocytes, reflecting the systemic energy homeostasis of the body [12]. Thus, the decrease in LDH levels after navigation is a sign of energy potential depletion.

Creatine phosphokinase (CK) is an enzyme that catalyzes the transfer of a phosphate group from ATP to creatine, resulting in the formation of creatine phosphate and ADP. CK is an enzyme of urgent adaptation and the production of the membrane protector—neoton (creatine phosphate)—and can influence the blood coagulation system through ADP. Any physical exertion and even mild stress can be accompanied by a sharp increase in CK activity. In crew members after navigation, the level of CK significantly increases (p=0.001), which may be related to physical exertion and the impact of stressful situations during the navigation period.

Since the enzyme ALT (alanine aminotransferase) is an indicator of gluconeogenesis, its observed increase in crew members after navigation compared to baseline data further confirms the activation of gluconeogenesis alongside the established increase in glucose levels. The median value of ALT after navigation is 26.5 U/L, with an ideal reference value of 20.0 U/L. It should be noted that ALT is also a key marker of anabolism.

The fact that the median ratio of AST to ALT (KDR) after the voyage is only 0.89 (0.73; 1.14) and is significantly lower (p=0.000) than the normal range (1.3 – 1.5) indicates a predominance of anabolism, i.e., it is characterized by the activation of restorative processes after intense losses during the navigation period. In a healthy organism, catabolism should slightly prevail over anabolism. The predominance of anabolism over catabolism observed in crew members after navigation indicates significant depletion of the crew members' bodies during prolonged navigation.

The next dynamic enzyme that shows a significant increase after the voyage compared to baseline is ALP (alkaline phosphatase) (p=0.000). ALP raises the level of phosphates in the blood, contributes to acidosis, and as a membrane enzyme, it releases glucose from tissues by cleaving the phosphate group [13]. ALP is a fundamental metabolite for all bioenergetics (the phosphate-extracting mechanism of mitochondria) and the synthetic component (all metabolic processes begin with the phosphorylation of substrates) of the entire metabolism. The significant increase in ALP levels indicates processes aimed at replenishing bioenergetics that were depleted during prolonged navigation; it may also be associated with elevated glucose levels.

GGT (gamma-glutamyl transferase) is an enzyme involved in the transmembrane transport of amino acids, with its main function being adaptation to protein starvation under various normal and pathological conditions of the body. Any increase in GGT levels (reference level 20 U/L) indicates episodic or constant borrowing of amino acids from cellular pools. GGT is part of the glutathione antioxidant system, and its role sharply increases under any stress, making it highly inducible and responsive to external influences. From the perspective of classical metabolic regulation theory, its ultimate goal is to maintain energy homeostasis, which is achieved through the intensification of gluconeogenesis, utilizing necessary substrates with the help of ALP and GGT [13]. The level of GGT activity is equal to that of ALT [5], which is also observed in our study. Additionally, the observed trend towards a decrease in total protein levels (p=0.063) after navigation is an additional sign of the borrowing of amino acids from cellular pools.

Conclusion
Thus, the results of our comparative analysis of blood biochemical parameters indicate that, by the end of prolonged navigation, crew members show significant shifts compared to baseline data. The increased levels of glucose and ALT, along with normal cholesterol levels, suggest an enhancement of gluconeogenesis processes; the low level of LDH, high levels of creatinine, CK, GGT, ALP, and the AST/ALT ratio indicate processes aimed at restoring energy potential through the activation of amino acid borrowing from tissues, a compensatory predominance of anabolism over catabolism, and the activation of antioxidant defenses. This ultimately demonstrates the negative impact of prolonged navigation on the bodies of crew members and the high risk of developing maladaptive metabolic disorders.