Relevance. In light of the popularization of the use of caffeine-containing products, the question of the combined use of caffeine with substances exhibiting a toxic effect remains open. The doses of caffeine, which have a pronounced antidepressant effect, are also insufficiently studied. The aim of the study was to study the effect of repeated administration of caffeine and dioxidine on the behavioral responses of mice in the Porsolt test. Materials and methods. The experiment was carried out on 36 outbred male mice, divided into 6 groups. Experimental groups for 15 days of the study received caffeine at a dose of 40 mg/kg (first) or 100 mg/kg (second), dioxidine at a dose of 200 mg/kg (third), together with caffeine 40 mg/kg or 100 mg/kg, and dioxidine (fourth and fifth groups, respectively). The animals of the control group were injected with saline. To study the behavior, the Porsolt test was carried out, evaluating the following indicators on the 1st, 8th and 15th days of the experiment: the total time of immobilization, active swimming, climb, the number of grooming and shaking off acts. Results . The administration of caffeine at a dose of 40 mg/kg caused an increase in the time of active swimming and a decrease in the duration of immobilization on the 8th and 15th days. When caffeine was used at a dose of 100 mg/kg, an increase in the time of active swimming was noted with a single exposure, with an experiment duration of 8-15 days, an increase in the duration of immobilization was observed. Dioxidine caused a significant decrease in the time of active swimming and an increase in the duration of immobilization during all days of the experiment. The combined use of caffeine (40 mg/kg and 100 mg/kg) and dioxidine on the 1st day led to a decrease in immobilization and the time of active swimming. In both groups, 100 % animal mortality was observed by the 15th day. Conclusion. The results of the study indicate the presence of an antidepressant effect in caffeine at a dose of 40 mg/kg on the 8th and 15th days of the experiment and the absence of this effect in caffeine at a dose of 100 mg/kg with a duration of administration of 8-15 days. The use of dioxidine led to the absence of antidepressant activity and the presence of the opposite effect. The combined administration of caffeine (40 mg/kg and 100 mg/kg) and dioxidine led to 100 % mortality in the experimental groups by the 15th day of the experiment
Введение. Патологическое повышение активности свертывающей системы вызывает нарушение реологических свойствкрови, является фактором риска развития тромбоза крупных сосудов и возникновения ишемической болезни сердца, инфаркта миокарда, тромбофилии и ДВС-синдрома. Цель исследования: изучение влияния светового десинхроноза на функциональную активность коагуляционного механизма гемостаза в эксперименте. Материалы и методы. Экспериментальное исследование было выполнено на 36 нелинейных самцах белых крыс, разделенных на 3 группы: контрольную группу, не подвергавшуюся воздействию светового десинхроноза, и 2 опытных, находившихся в условиях искусственного освещения на протяжении 10 и 21 суток, соответственно. Состояние коагуляционного звена системы гемостаза оценивали по следующим показателям: активированное частичное тромбопластиновое время, протромбиновое время и концентрация фибриногена. Антикоагулянтную активность крови оценивали путем определения активности в плазме крови антитромбина III. Состояние фибринолитической системы оценивали по концентрации в плазме растворимых фибрин-мономерных комплексов и D-димеров. Для динамической оценки активности тромбина применяли тест генерации тромбина. Результаты. Установлено негативное влияние светового десинхроноза на состояние гемостаза. На 10-е сутки эксперимента выявлено компенсаторное повышение активности противосвертывающей и фибринолитической систем. Нахождение подопытных животных в условиях длительной световой депривации на протяжении 21 суток способствовало развитию стресса и сдвигу системы гемостаза в сторону гиперкоагуляции. Заключение. Результаты проведенного экспериментального исследования позволяют сделать вывод о возникновении стресс-реакции у подопытных животных под воздействием светового десинхроноза, а также о гиперкоагуляционных нарушениях равновесия в системе гемостаза, что создает предпосылки для формирования тромбинемии. Background. A pathological increasing of coagulation activity causes disorders of blood rheological properties, that is a risk factor for large vessels thrombosis and coronary heart disease, myocardial infarction, thrombophilia and disseminated intravascular coagulation. Objectives: to study the effect of light desynchronosis on the functional activity of hemostasis coagulation mechanism in experiment. Materials/Methods. The experimental study was carried out on 36 nonlinear male white rats, divided into 3 groups: a control group that was not exposed to light desynchronosis, and 2 experimental groups under artificial lighting for 10 and 21 days, respectively. Coagulation hemostasis was assessed by following parameters: activated partial thromboplastin time, prothrombin time, and fibrinogen content. Anticoagulant blood activity was assessed by antithrombin III activity. Plasma levels of soluble fibrin-monomeric complexes and D-dimers were used for fibrinolytic system assessment. The thrombin generation assay was used for thrombin activity assessment. Results. Light desynchronosis negatively impact hemostasis. On the 10th day of the experiment we revealed a compensatory increasing of anticoagulant and fibrinolytic activities. Exposure of experimental animals to prolonged light deprivation for 21 days caused stress development and hemostasis shift towards hypercoagulation. Conclusions. Light desynchronosis leads to stress reaction in experimental animals as well as to hypercoagulable hemostasis disorders that creates the preconditions for thrombinemia.
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