M. V. Khrapova, O. S. Bryushinina, Yu. G. Zyuzkova, N. V. Kandalintseva, E. B. Menshchikova
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引用次数: 0
Abstract
TS-13 (sodium 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate) is a synthetic antioxidant that in numerous studies has demonstrated biological effectiveness in modeling pathological conditions in vivo, in particular, in the model of Parkinson’s disease. To establish whether these effects are indirect or associated with, among other things, the direct effect of TS-13 on the organs and tissues of animals, in this work we determined the concentration of TS-13 in the blood plasma and brain of rats after intragastric administration. After a single intragastric injection of TS-13 solution at a dose of 100 mg/kg to male Sprague Dawley rats (n = 57), biomaterial (blood, brain) was collected over 24 h. To measure the concentration of a substance in samples, a bioanalytical technique using high-performance liquid chromatography with UV detection was developed and validated. The quantitative determination method was developed by us for the first time and validated before the study. It has been established that the calculated values of the calibration samples meet the acceptance criteria (have the required accuracy and precision) in the concentration range from 0.05 to 6 μg/mL, R = 0.9998. The results of determining the concentration of TS-13 in the blood plasma and brain of rats showed that after a single oral administration the compound enters the blood, where it is detected within 15 h (average retention time 7.94 h, half-life 7.59 h, elimination constant 0.13 h–1, total clearance 40.1 L/(kg h)), and also penetrates the blood–brain barrier, quickly entering the brain (maximum concentration is achieved after 1 h). The compound has low affinity for brain tissue (tissue availability 0.32), and, therefore, its concentration does not reach high values; however, slow elimination of the substance is observed—average retention time 6.56 h, half-life 6.43 h, elimination constant 0.11 h–1. After a single intragastric administration to rats, TS-13 enters the blood, where at least part of it is detected unchanged after 30 min, reaching maximum values after 1 h. A similar kinetics of the substance is characteristic of the brain, where it is found in smaller quantities. Thus, as a result of the study, it was shown that TS-13 penetrates the blood–brain barrier and is able to directly affect brain structures, which, however, does not negate the possibility of an indirect effect, mediated by the ability to change the activity of intra- and intercellular signaling systems.
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The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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