Yelena Valerievna Yepifantseva
◽
Mayra Galimzhanovna Abdrakhmanova
◽
Yelena Vladimirovna Pozdnyakova
◽
Polina Sergeyevna Semenikhina
◽
Ruslan Andreevich Belyayev
◽
...
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.”
Sildenafil alters biogenic amines and increases oxidative damage in brain regions of insulin-hypoglycemic rats
