BACKGROUND: Prolonged exposure to stress is known to change homeostasis and can lead to the development of psychopathological disorders, including depression. Exposure to stress factors contributes to the emergence of reactive oxygen species in the brain. The data characterizing changes of the oxidative metabolism under conditions of chronic stress are insufficient, which determine the relevance of the research in this direction. The determination of reactive carbonyl derivatives of proteins (RCDP), methylglyoxal (MG), and malondialdehyde (MDA) levels can be considered an informative method for studying the dynamics of oxidative metabolism. AIM: The aim of the study was to study the RCDP, MG, and MDA in red blood cells and blood plasma in rats experiencing chronic unpredictable moderate stress (CUMS). METHODS: A total of 20 male outbred rats weighing 450–500 g were used in the study. The animals were divided into two groups of ten rats each using randomized selection. The experimental group of animals was exposed to the impact of diverse stress factors, according to the CUMS model for 21 days. The control group of animals remained in standard conditions and did not undergo CUMS model. Blood sampling was performed twice for all rats the day before the experiment started and on 21st day to determine the level of RCDP, MG, and MDA in their erythrocytes and blood plasma. RESULTS: The study revealed a significant decrease of RCDP (p = 0.007) and MDA levels in erythrocytes (p = 0.013), and MDA level in blood plasma (p = 0.005) of rats of the main experimental group. The control group showed a significant increase of RCDP level in plasma (p = 0.008), a two-fold increase of MDA in erythrocytes (p = 0.05) with a decrease of MDA in plasma (p = 0.011). A tendency for MG increase was noted in erythrocytes of rats in both the main group and the control group. CONCLUSION: The early stages of CUMS were accompanied by the violation of oxidative metabolism with the emergence and accumulation of RCDP and MDA in the blood of animals. The decreased emergence of RCDP and MDA in the later stages can be associated with an excess of oxidized substrates in the blood of animals of the experimental group. The revealed trend toward MG growth in animals of both groups suggests its increased synthesis in erythrocytes, which, in our opinion, should be considered a negative factor affecting the deformability of red cells. In turn, a violation of the deformability of red blood cells leads to a violation of microcapillary blood flow, which contributes to the development of hypoxic damage in different tissues. Thus, the obtained data confirm the different directions of changes in RCDP and MDA levels in the blood of animals experiencing CUMS or acute stress. Our results prove the need for further research on changes in oxidative metabolism in chronic stress disorders.

BACKGROUND: Understanding the mechanisms of the behavioral disorders’ emergence under the influence of chronic stress is the most important aspect of the subsequent development of a strategy for its therapy and prevention. Changes in the oxidative metabolism processes can be decisive in the development of the pathogenetic cascade in the brain. Information about these processes can be obtained by studying protein carbonylation, lipid peroxidation, and catalase activity (CA). The complexity of the therapeutic impact in various behavioral disorders implies the search for new pharmacological substances and the study of the previously known drugs’ effects based on the available scientific data. AIM: The aim of the study was to study the reactive carbonyl derivatives of proteins (RCDP), malondialdehyde (MDA), and CA in the brain of rats after therapy following chronic unpredictable moderate stress (CUMS). METHODS: Forty male outbred rats weighing 450–500 g were used in this study. For 21 days, all animals were exposed to the diverse stress factors for developing the CUMS. The animals were divided into four groups of 10 rats, each using randomized selection. The rats of one group were euthanized by decapitation with subsequent brain harvesting (Group 4). Remaining three groups of rats were treated with placebo (Group 1), harmine hydrochloride (Group 2), and amitriptyline (Group 3) for 21 days. Upon completion of therapy, all rats were also euthanized by decapitation with subsequent brain harvesting. The levels of RCDP, MDA, and CA were studied in their brain, and after that, we compared the multiple studied indicators in four groups. RESULTS: The results of the rat brain examinations in four groups showed that RCDP level in Group 2 was significantly lower than in Group 4 (p = 0.000). Similarly, in Group 1, it was lower than in Group 4 (p = 0.021), plus, it did not differ statistically from the harmine hydrochloride group (p = 1,000). Indicators of Groups 3 and 4 did not have any significant differences in RCDP level, too, (p = 0.799); however, the RCDP level in Group 2 was significantly lower than in Group 3 (p = 0.040). MDA indicators did not show significant differences; however, a tendency for lower values was revealed in Group 1 (p = 0.233) and Group 2 (p = 0.151). CA in Group 4 was lower than that in Group 1 (p = 0.000), Group 2 (p = 0.001), and Group 3 (p = 0.003) contemporaneously, while all treatment groups were comparable (p = 1.000). CONCLUSION: The result of exposure to chronic stress can be reproduced with the best quality in the CUMS model. The neurobiological foundations of the model make it possible to assess biochemical markers of oxidative metabolism and evaluate the possibilities of pharmacological correction of stress-induced behavioral disorders. To assess the mechanisms of autoregulation of oxidative metabolism, this study included a placebo group (Group 1), the level of RCDP in which was significantly higher in comparison with Group 3 and Group 4 and slightly lower than in Group 2. In this study, harmine hydrochloride demonstrated activity exceeding amitriptyline, particularly limiting the process of protein carbonylation, not noted for amitriptyline. According to the results of the RCDP assessment in the CUMS model, the process of protein carbonylation can be considered to be one of the significant factors in the deactivation of neurotransmitters. The CA levels determined in all groups allowed us to consider this marker as the most sensitive to the effects of stress, which possibly has an inhibitory effect on catalase, as its activity in all groups after therapy was more than two-fold higher than in animals right after CUMS. We can assume that CA plays an important role in starting the processes of autoregulation of oxidative metabolism. The study was carried out as a part of the implementation of the scientific and technical program No. BR05236584 “Development of new herbal preparations and their pharmacological and clinical studies” (O.0820). (2018–2020) in the priority area, “Life and Health Sciences.”

Introduction: As a full-fledged Bologna process participant, Kazakhstan is continuously implementing reforms aimed at medical education, impacting country's human capital. The professional capable of a lifelong learning is the main goal of modern education. The central role in reaching this goal is entrusted to the higher education. The relevance of our study lies within the curriculum changes with more hours for students’ independent work, which is the main method of obtaining reliable information and acquiring competence for lifelong learning. The aim of our study was to evaluate the students’ opinion on the self-study system at the Karaganda Medical University, revealing existing difficulties in the students’ acceptance of the Bologna process requirements, identifying methods to increase their involvement in self-education and scientific research. Materials and Methods: an anonymous survey was conducted among the 426 of the 3rd – 7th year and residency students, including 20 questions to identify students’ attitude to the individual work methodology as a factor for the development of skills for lifelong learning. Results and Discussion: the majority of students are voluntarily involved in the independent learning, understand its purpose, and use English-language sources with reliable up-to-date information. Less than half of the students evaluate their skills of information search and presentation as «average» and only about a quarter of them as «high». More than half of the students demonstrate interest in increasing their level of competence with these skills. Conclusions: Our study demonstrated that since the Republic of Kazakhstan accession to the BP the «Karaganda Medical University» successfully integrates new educational requirements into the educational process. Higher education system needs further improvement to better understand the students, remove barriers to progress and preserve students’ motivation to further develop personal potential.