Effects of Gly-His-Lys-D-Ala Peptide on Skin Wound Regeneration Processes.

We evaluated the effects of the Gly-His-Lys-D-Ala peptide in a dose 0.5 µg/kg on skin wound regeneration in male Wistar rats (n=80) after initial surgical debridement when administered intracutaneously around the site of injury. Histological (severity of the inflammatory reaction, formation of granulation tissue, and epithelialization terms) and morphometric (number of fibroblastic cells, macrophages, granulocytes, and lymphocytes) studies were performed on autopsy specimens on days 3, 7, 10, and 30 of the experiment. Daily intracutaneous injection of the peptide resulted in an increase in the number of fibroblastic cells and macrophages, as well as in a decrease in the number of granulocytes against the background of active wound contraction on day 30 of the experiment. Thus, Gly-His-Lys-D-Ala alleviated the inflammatory reaction and promoted the regenerative processes.

Reparative and Antioxidant Effects of New Analogues of Immunomodulator Thymogen in Experimental Model of Liver Damage.

We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule.

Effects of ACTH6-9-Pro-Gly-Pro Peptide on the Levels of Pro- and Anti-Inflammatory Cytokines in Wistar Rats under Conditions of Chronic Restraint Stress.

We evaluated the effect of ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide on the serum levels of pro- and anti-inflammatory cytokines in experimental animals under conditions of chronic restraint stress. Stress exposure over 2 weeks led to an increase in the levels of IL-1ß, IL-6, and IFNγ in rats. Daily intraperitoneal injection of ACTH6-9-PGP in a dose of 5 µg/kg before stress exposure significantly decreased the levels of IL-6 and IFNγ by 4.8 and 49.3% respectively. Administration of the peptide in a dose of 50 µg/kg decreased the levels of IL-1ß and IFNγ by 51.2 and 39.7%, respectively. However, no changes in the cytokine levels were observed after injection of the peptide in a dose of 500 µg/kg. Thus, ACTH6-9-PGP administered in doses of 5 and 50 µg/kg prevented the stress-induced changes in the levels of pro- and inflammatory cytokines.

Morphological changes in immune and endocrine organs of stressed mice after administration of a gonadotropin-releasing hormone analogue.

Administration of Surfagon, a gonadotropin-releasing hormone analogue, in doses of 0.1 and 5.0 microg/kg before emotional nociceptive stress increased lymphocyte migration from the thymus, decreased the volume of lymphoid tissue in the spleen and thymus, reduced the width of the zona fasciculata and increased the width of the zona glomerulosa in the adrenal cortex of male CBA mice. These effects of the peptide persisted in castrated animals. Surfagon prevented stress-induced activation of the adrenal glands and accidental transformation of the thymus and spleen in castrated animals.

Effect of gonadotropin-releasing hormone analogue on thermal nociception in mice.

Intraperitoneal treatment with an analogue of gonadotropin-releasing hormone in doses of 0.004-450 microg/kg produced an analgesic effect on male mice in the hot plate test. Castration significantly elevated the nociceptive thresholds. In castrated mice the effects of the test peptide were less pronounced and had an algesic nature. Our results indicate that these effects depend on functional activity of the hypothalamic-pituitary-gonadal axis.

[Effect of the intraventricular administration of gonadotropin-releasing hormone analogue on immune response and unspecific resistance in rats].

Intraventricular administration of the synthetic analogue of gonadotropin-releasing hormone (surfagon) results in increased humoral immune response and neutrophile activation including phagocytic and special functional indices in rats. Since testosterone blood level is not changed it may be concluded that the surfagon effect is mediated by nervous mechanisms. The conclusion is also confirmed by the obtained data of the brain stress-limiting system activation manifested by the decrease of oxidative stress.

Morphological changes in immune and endocrine organs of mice injected with a gonadotropin-releasing hormone analog.

Infection of surfagon (gonadotropin-releasing hormone analog) in a dose of 0.1 microg/kg to male CBA mice stimulated lymphocyte migration from splenic B zones, caused moderate thinning of the thymic cortex, thickening of the zona fasciculata of the adrenal cortex with signs of corticocyte activation. After administration of 5 microg/kg surfagon we observed alteration of the splenic T zone, drastic thinning of the thymic cortex, and extension of the zona glomeruloza in the adrenal cortex. These effects were retained after castration, which attests to their steroid-independent nature.

[The effect of the synthetic analogue of gonadoliberin on immune response and factors of nonspecific resistance in rats and mice]. / Vliianie sinteticheskogo analoga gonadoliberina na immunnyi otvet i faktory nespetsificheskoi rezistentnosti u krys i myshei.

Gonadotropin-releasing hormone's synthetic analogue (surfagon) injected intraperitoneally exerted a dose-dependent influence on humoral immune response values in rats and on phagocytic and functional activity of neutrophiles in mice. Castration induced a reliable decrease of the immune response and character. It may be concluded that the surfagon effect is not mediated by steroids.

Immunotropic effects of gonadotropin-releasing hormone analog under conditions of emotional painful stress.

Surfagon, a synthetic analog of gonadotropin-releasing hormone injected before emotional painful stress dose-dependently changed the number of antibody-producing cells in rats and phagocytic and functional activities of neutrophils in mice. In castrated animals this peptide increased all studied parameters. This suggests that sex steroids are not involved in the realization of these effects.

[Effect of a luliberine analogue (surfagon) on food conditioning in rats with different sensitivity to ethanol]. / Vliianie analoga liuliberina (surfagona) na vyrabotku pishchevogo uslovnogo refleksa u krys s razlichnoi chuvstvitel'nost'iu k étanolu.

Food conditioning worsened following a luliberine analogue surfagon administration in short-sleeping (SS) rats. Castration mostly inhibited the peptide effect. The findings suggest a possibility of the peptide effect occurring even without steroids.

[The effect of a luliberin analog on the formation of alcoholic motivation in rats]. / Vliianie analoga luliberina na formirovanie alkogol'noi motivatsii u krys.

The synthetic luliberin analogue-agonist surfagon exerted a dose-dependent activating effect on formation of alcoholic motivation in white male rats. No such effect occurred in castrated rats, even though the rate of alcohol consumption was higher in the latters. The data obtained suggest a steroid-dependent mechanism of surfagon.

[Neurotropic effects of luliberin analog in rats with different sensitivity to ethanol]. / Neirotropnye éffekty analoga liuliberina u krys s razlichnoi chuvstvitel'nost'iu k étanolu.

Luliberin's analogue (surfagon) has been established to activate shock-induced aggression of short-sleeping (SS) and long-sleeping (LS) rats in painful stress. The using of the castration and hypophysectomy has proved this effect to result from the direct neurotropic action of peptide. It has been shown, that SS rats differ from LS ones by more expressed reducing of painful aggressive and reference reactions after castration and hypophysectomy as well as by definitive peculiarities of peptidergic effects of surfagon.