The antioxidant system activity during normal pregnancy and pregnancy following by hypoxic stress Pregnancy in mammals is characterized by an increase in basal oxygen consumption, as it develops there is an increase in oxidative stress while in pregnancy complicated by hypoxic stress the oxidative damage enhances. The oxidative stress during prenatal development seems to be one of the key factors in the pathogenesis of most pregnancy disorders, including preterm birth and preeclampsia. The growing demand for oxygen increases either the production of reactive oxygen species or the synthesis of antioxidant defense components. To assess the antioxidant defense activity in rats, the content of non-protein thiols in the blood and liver homogenate, catalase activity in liver homogenate, superoxide dismutase activity in blood plasma and liver homogenate, total antioxidant activity in blood plasma, and the intensity of lipid peroxidation in blood plasma and liver homogenate were determined. According to data obtained a decrease in antioxidant defense activity in blood plasma and liver of females is shown in the prenatal period of normal pregnancy and, particularly, in the same period of pregnancy complicated by hypoxic stress. It can be assumed that changes in blood antioxidant defense parameters reflect changes not only in mother’s body, but also in placenta, providing potential danger to the developing fetus.

Melanocortins (MCs) have a wide spectrum of physiological activity. All native MCs have a core pharmacophore structure of tetrapeptide His-Phe-Arg-Trp sequence, corresponding to ACTH6-9 fragment. The sequence is necessary for activation of all subtypes of MC receptors, but the tetrapeptide has poor potency and selectivity. It was shown earlier that the addition of proline-rich sequences to natural peptides led to enhancing and prolongation of their neurotropic effects. An example of such a compound is fragment ACTH4-10 analog with prolong neurotropic effects heptapeptide Semax (ACTH4-7Pro-Gly-Pro). The work is devoted to the research of the effects of a synthetic peptide comprising the natural ACTH6-9 sequence and the fragment PGP in its structure – ACTH6-9PGP (HFRWPGP). The peptide effects on the learning ability and anxiety level were studied in white rats. The peptide was injected intranasally at a dose of 0.05 mg/kg 15 min or 20 h before the experiment. It was shown that heptapeptide ACTH6-9PGP improved the acquisition of food-motivated maze task and retention of passive avoidance task, and also it exhibited an anxiolytic activity in elevated plus maze test when injected 15 min before testing. The peptide administration 20 h before testing did not lead to changes in learning parameters and anxiety level in comparison to control animals. Thus, the peptide the structure of which includes ACTH6-9 fragment and tripeptide PGP has nootropic and anxiolytic activity. Consequently, the spectrum of neurotropic activity of ACTH6-9PGP coincides with the spectrum of Semax activity, but the duration of its effects is much shorter.

The combined effect of Semax with water solutions of plumbum diacetate (10–7 M) and ammonium molybdate (10–5 M) on the two-way active avoidance learning in rats in the shuttle chamber was studied. It was established that both salts of heavy metals oppress the learning and memory; plumbum diacetate caused larger oppression. Semax slowed down the development of the conditioned response but counteracted the negative influence on this process from the side of both metals. The effect of Semax on the development of the avoidance reaction in the presence of ammonium molybdate, which oppressed the avoidance by itself, paradoxically intensified. During the combined effect of the peptide and ammonium molybdate, the development of the conditioned reaction occurred much faster than against the background of Semax without the combination with molybdenum. In total, data obtained indicate a counteraction of Semax to neurotoxic effect of plumbum and molybdenum salts. Since oxidative stress is the main mechanism of neurotoxic effect of heavy metals, the indicated positive effect of Semax can, in our opinion, confirm the presence of antioxidant properties in the spectrum of the peptide pharmacological activity.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined in male Wistar rats with normal body weight or alimentary obesity. In normal rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2 fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated less pronounced risk-taking behavior and elevated nociceptive threshold in comparison with normal animals, but these differences were abolished by chronic administration of FNAP-NH2.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

The effects of Semax on the formation of a conditioned active avoidance reaction were studied in rats using different experimental models. I.p. administration of Semax at a dose of 0.05 mg/kg was found to accelerate the acquisition of a one-way conditioned avoidance reaction in a model of an active pain stimulus avoidance reflex in which the animals had to jump onto a shelf. In animals trained in a shuttle box, the peptide increased the threshold current required to provoked movement of the rats across the chamber and slowed acquisition of a two-way active avoidance reaction. Semax stimulated reproduction of the avoidance reaction in the shuttle box in rats after functional impairment induced by acute changes in cause-effect and spatial relationships in the experimental environment. These data support the view that this peptide has nootropic properties.

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.