Intraperitoneal injection of Semax (synthetic analogue of ACTH4-7, MEHFPGP) in a dose of 50 mg/kg produced a protective effect on rats with experimental indomethacin-induced ulcers. Experiments on narcotized rats showed that Semax in the studied dose had no effect on basal blood flow in the stomach, but prevented reduction of blood flow induced by indomethacin. The antiulcer effect of Semax is probably related to improvement of blood flow in the gastric wall disturbed by indomethacin.
The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1-β-D-eritrofuranozyl uracil and 3'-O-β-D-ribofuranosyl-2'-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-β-D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.
One of the most urgent and important tasks of modern biological and medical research is the search and research of pharmacological agents that combine lipid-lowering and antithrombotic effects in the organism. The unique effects of the regulatory peptides of the oxoproline series (5-oхo-Pro-His-Pro-NH2, 5-oxo-Pro-Trp-Pro and 5-oxo-Pro-Arg-Pro or 5-oхo-Pro-His-Pro-NH2, Pyr-Trp-Pro and Pyr-Arg-Pro) have been found in rats with hypercholesterolemia (metabolic syndrome). Multiple intranasal of these peptides to animals with developed hypercholesterolemia increased anticoagulant, fibrinolytic and antiplatelet potential of the blood and simultaneously lowered increased concentrations of total cholesterol, low-density lipoprotein cholesterol and triglycerides. In addition, they contributed to the normalization of blood glucose levels. A week after the last admistration of these peptides, the hypocholesterolemic, normoglycemic and anticoagulant effects persisted. The relationship between the structure of peptides of the oxoproline series and their functional properties is discussed. A conclusion is made about the prospects of further studies of oxoproline peptides as drugs that combine antithrombotic effects with the improvement of fat metabolism in the body.
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