Atherosclerosis has recently been associated with pathological processes occurring in the vascular endothelium. The efficacy of antiatherosclerotic drugs is consequently determined by their capability of pro� tecting the vascular wall (1, 2). In view of this, trietha� nol ammonium salts of aroxiacetic acids with a pro� tatrane structure (3) attract particular attention, since these compounds reduce damage to elastic fibers and stabilize cell membranes (4). The new drug Trekresan (TK, cresacin), which has been developed in the Irkutsk Institute of Chemistry (Siberian Branch, Rus� sian Academy of Sciences), is of particular interest, since this drug exerts a broad range of therapeutic effects according to our earlier study (5). Recent studies have elucidated the atherogenesis� controlling mechanisms that are related to cytokine activity of certain protein factors. A role has been demonstrated for enzymes belonging to aminoacyl� tRNA synthetases, which perform key functions in metabolism. When cleaved, tyrosyltRNA synthetase (TyrRS) possesses cytokine activity and stimulates angiogenesis, thus facilitating atherogenesis (6, 7). TryptophanyltRNA synthase (TrpRS), which is homologous to TyrRS, occurs in two forms in the cell. The major form is full size, while a minor form is trun� cated (miniTrpRS), lacking an Nterminal fragment as a result of alternative splicing associated with pre� mRNA maturation (8). Certain protein factors, such as interferon γ, dramatically increase the production of the two forms of the enzyme in all mammals. In contrast to TyrRS, TrpRS and, especially, miniTrpRS exert distinct antiangiogenic and antiatherogenic effects (6, 7). Therefore, the molecular mechanisms of TK action may be inferred from the dynamics of TrpRS activity. The objective of this work was to study in detail the effects of TK on the development of experimental atherosclerosis and TrpRS activity. TK effects were experimentally studied in rabbits weighing 2.5-3.0 kg. Atherosclerosis was modeled according to Anichkov and Khalatov by daily adding cholesterol to the rabbits' diet at 0.25 g/kg body weight. One month after the start of the experiment, the rabbits were tested for blood cholesterol, total lip� ids, triglycerides, and β�lipoproteins. Based on the results, the rabbits were divided into test and control groups. All rabbits continued receiving cholesterol. Rabbits of the test groups were treated with TK, while rabbits of the control groups received saline. In the first series of experiments, rabbits were intramuscu� larly injected with TK (an extemporaneous aqueous solution) at 5 mg/kg body weigh daily for 2 months. In the second series, TK was injected similarly but at 25 mg/kg body weight. In the third series, TK was added to the rabbits' diet at 50 mg/kg body weight daily for 2 months. In the fourth series, TK was added similarly but at 150 mg/kg body weight daily. In the fifth series, rabbits were intramuscularly injected with TK at 5 mg/kg body weight from the first day of the experiment; i.e., TK treatment started together with cholesterol treatment. The experiments were carried out for 3 months. The rabbits were sacrificed by air embolism. At the end of the experiments, rabbits were tested for the levels of cholesterol, total lipids, triglyc� erides, and β�lipoproteins in the venous blood serum by standard methods; the cholesterol and triglyceride levels in the liver; the lipid and cholesterol contents in the thoracic aorta; and the index of atherosclerotic lesions in the thoracic aorta.
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Jan 1, 2023
V V Bykov + 6
Open Access