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1.
Dokl Biochem Biophys ; 497(1): 104-107, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33895924

RESUMO

The cytotoxicity of doxorubicin (Dox) and its peptide modifications Z-Gly-Pro-Dox and Boc-Gly-Pro-Dox were studied. Tetrahymena pyriformis was used as a test system, which made it possible, due to the short life cycle and high reproduction rate of ciliates, to trace their response to the effects of toxicants over several generations. It was found that peptide modification of the Dox molecule markedly reduces its cytotoxic and cytostatic effect. The Z-Gly-Pro-Dox modification has less cytotoxic and cytostatic effect compared to Boc-Gly-Pro-Dox. When determining the ability of drugs (at a concentration of 100 µM) to prevent bacterial contamination of samples, it was shown that the smallest degree of overgrowth was recorded in the presence of Dox (OD600nm 81.1). Boc-Gly-Pro-Dox also had a bacteriostatic effect, though less pronounced (OD600nm 93.8). The degree of overgrowth in the presence of Z-Gly-Pro-Dox was close to that of distilled water. The results obtained on ciliates did not contradict the data obtained in similar studies on mice.


Assuntos
Citotoxinas/química , Citotoxinas/toxicidade , Doxorrubicina/química , Doxorrubicina/toxicidade , Peptídeos/química , Tetrahymena pyriformis/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Camundongos , Relação Estrutura-Atividade
2.
Bull Exp Biol Med ; 170(3): 384-388, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33459919

RESUMO

We studied the effect of intraperitoneal administration ACTH(4-7)-PGP in doses of 5, 50, 150, and 450 µg/kg to Wistar male rats 12-15 min before modeling restraint stress on the morphofunctional state of the colon. In rats exposed to restraint stress, signs of atrophy and inflammatory reaction in the colon wall, changes in functional activity and number of mast cells, and increased serum level of corticosterone were observed. Administration of the peptide led to a decrease in corticosterone concentration, alleviated stress-induced pathomorphological changes, and promoted adaptation of the intestinal wall to stress. The positive effects of ACTH(4-7)-PGP can be determined by multifunctional nature of the physiological and pharmacological effects of the neuropeptide.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Fragmentos de Peptídeos/farmacologia , Restrição Física/efeitos adversos , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/farmacologia , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Corticosterona/sangue , Masculino , Ratos , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos
3.
Bull Exp Biol Med ; 169(6): 775-777, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33098507

RESUMO

Anticoagulant effects of 12 short peptides of the glyproline series - Arg-Glu-Arg-Pro-Gly-Pro (RERPGP), Arg-Glu-Arg-Val-Gly-Pro (RERVGP), Arg-Glu-Arg-Gly-Pro (RERGP), Arg-Pro-Gly-Pro (RPGP), Pro-Leu-Pro (PLP), Pro-Leu-Pro-Ala (PLPA), Pro-Gly-Pro-Leu (PGPL), Phe-Pro-Leu-Pro-Ala (FPLPA), Pyr-Arg-Pro (PyrRP), Lys-Lys-Arg-Arg-Pro-Gly-Pro (KKRRPGP), Arg-Lys-Lys-Arg-Pro-Gly-Pro (RKKRPGP), and Lys-Arg-Lys-Pro-Gly-Pro (KRKPGP) in concentrations of 10-3 and 10-2 mg/ml in vitro was demonstrated by the thromboelastographic method. The effects of 6 peptides ((RERPGP, RPGP, PLP, PLPA, RKKRPGP, and KKRRPGP) were also observed in vivo after intranasal or oral administration. Changes in the studied thromboelastographic parameters towards hypocoagulation in comparison with the control group were noted. Arginine and leucine glyprolines produced the maximum anticoagulant effect.


Assuntos
Anticoagulantes/sangue , Arginina/química , Leucina/química , Lisina/química , Oligopeptídeos/sangue , Administração Intranasal , Administração Oral , Sequência de Aminoácidos , Animais , Anticoagulantes/síntese química , Masculino , Oligopeptídeos/síntese química , Tempo de Tromboplastina Parcial , Ratos , Tromboelastografia/métodos , Tempo de Coagulação do Sangue Total
4.
Bull Exp Biol Med ; 169(3): 357-360, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32737723

RESUMO

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 µg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 µg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Colo/efeitos dos fármacos , Colo/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Restrição Física , Estresse Fisiológico/efeitos dos fármacos
5.
Bull Exp Biol Med ; 169(2): 281-285, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32651826

RESUMO

We studied the effects of Selank on the condition of the colon wall in Wistar male rats subjected to restraint stress. Selank was injected intraperitoneally in doses of 80, 250, and 750 µg/kg 15 min before stress exposure. In rats subjected to stress, signs of atrophy, inflammatory reaction, and changes in the number and functional activity of mast cells were observed against the background of increased corticosterone level. Selank administration led to a decrease in corticosterone levels, reduced pathomorphological manifestations of stress exposure, and accelerated adaptation. These effects were presumably realized due to multifunctional biological effects of Selank.


Assuntos
Oligopeptídeos/uso terapêutico , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Corticosterona/metabolismo , Modelos Animais de Doenças , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Ratos , Ratos Wistar , Restrição Física , Estresse Fisiológico/efeitos dos fármacos
6.
Dokl Biochem Biophys ; 491(1): 62-66, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32483752

RESUMO

Glutamate (Glu) excitotoxicity, which accompanies brain ischemia or traumatic brain injury, is the leading mechanism of neuronal death. In the present work, we studied the effects of the peptides HFRWPGP (ACTH6-9PGP), KKRRPG, and PyrRP on the survival of cultured cortical neurons on the background of excitotoxic effect of Glu (100 µM). Biochemical (MTT/WST) and morphometric analyzes showed that, depending on the dose, ACTH6-9PGP and KKRRPGP protect neurons from the cells death, while PyrRP, conversely, enhances it. The neuroprotective effect of ACTH6-9PGP is accompanied by a slowdown in the development of delayed calcium dysregulation and synchronous mitochondrial depolarization. Among the studied peptides, only ACTH6-9PGP significantly increased the number of neurons that restored Ca2+ homeostasis after Glu was abolished. The influence of KKRRPGP was less pronounced, whereas PyrRP, on the contrary, reduced the number of neurons with low [Ca2+]i. Thus, this study revealed the high therapeutic significance of ACTH6-9PGP and allowed assessing the prospects for its possible clinical use.


Assuntos
Cálcio/metabolismo , Ácido Glutâmico/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Peptídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Homeostase , Potencial da Membrana Mitocondrial , Microscopia de Fluorescência , Mitocôndrias/metabolismo , Oligopeptídeos/química , Peptídeos/química , Ratos , Ratos Wistar
7.
Biomed Khim ; 65(6): 498-506, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876520

RESUMO

Boc-Gly-Pro-DP, Z-Gly-Pro-DP, LA-Gly-Pro-DP, Boc-Gly-Pro-Srt, Z-Gly-Pro-Srt were synthesized for the first time. The stability of these compounds in the presence of leucine aminopeptidase, carboxypeptidase Y, carboxypeptidase B and proline endopeptidase (PEP) was determined. It turned out that the compounds are stable in the presence of aminopeptidases and carboxypeptidases. In the presence of PEP, dopamine (DP) and serotonin (Srt) are cleaved from the synthesized preparations. Thus, new proline-containing Srt and DP derivatives were obtained, Srt and DP could be gradually released from them. This suggest the possibility of a prolonged action of these biologically active compounds on the vital activity of cells and, consequently, of the whole organism.


Assuntos
Dopamina/química , Prolina/química , Serotonina/química , Carboxipeptidases , Cinética , Leucil Aminopeptidase , Prolil Oligopeptidases , Serina Endopeptidases
8.
Bull Exp Biol Med ; 168(2): 250-253, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31776957

RESUMO

We studied the effect of chronic intranasal and peroral administration of a new peptide preparation AСTH15-18PGP in a dose of 100 mg/kg body weight on the state of vascular-platelet and plasma hemostasis in animals. It was found that this synthetic regulatory peptide administered intranasally can produce antiplatelet, anticoagulant, and antifibrin-stabilizing effects on the blood plasma in healthy rats. In both administration routes, the peptide induced activation of the anticoagulation system of the hemostasis by increasing enzymatic and non-enzymatic fibrinolysis; after intranasal administration, the fibrinolytic effects were more pronounced.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Anticoagulantes/farmacologia , Fibrinólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Oligopeptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Prolina/análogos & derivados , Hormônio Adrenocorticotrópico/análogos & derivados , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Masculino , Prolina/farmacologia , Ratos , Ratos Wistar
9.
Dokl Biochem Biophys ; 488(1): 354-356, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31768859

RESUMO

A mass spectrometric method has been developed for determining the content of dopamine and serotonin derivatives, which allows evaluating the efficiency of their penetration through artificial membranes depending on the structure of their peptide fragment. In this case, the diffusion of dopamine and serotonin derivatives through the membrane occurred as a result of competitive interactions. It was shown which compounds in this mixture more easily penetrate through artificial membranes. It was found that the most promising in terms of overcoming the BBB are Boc-Pro-Srt and Boc-Pro-DOPA.


Assuntos
Dopamina , Membranas Artificiais , Peptídeos , Serotonina , Barreira Hematoencefálica/química , Barreira Hematoencefálica/metabolismo , Dopamina/análogos & derivados , Dopamina/química , Dopamina/farmacocinética , Dopamina/farmacologia , Humanos , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologia , Serotonina/análogos & derivados , Serotonina/química , Serotonina/farmacocinética , Serotonina/farmacologia
10.
Biochemistry (Mosc) ; 84(11): 1296-1305, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760919

RESUMO

Development of therapeutic preparations involves several steps, starting with the synthesis of chemical compounds and testing them in different models for selecting the most effective and safest ones to clinical trials and introduction into medical practice. Cultured animal cells (both primary and transformed) are commonly used as models for compound screening. However, cell models display a number of disadvantages, including insufficient standardization (primary cells) and disruption of cell genotypes (transformed cells). Generation of human induced pluripotent stem cells (IPSCs) offers new possibilities for the development of high-throughput test systems for screening potential therapeutic preparations with different activity spectra. Due to the capacity to differentiate into all cell types of an adult organism, IPSCs are a unique model that allows examining the activity and potential toxicity of tested compounds during the entire differentiation process in vitro. In this work, we demonstrated the efficiency of IPSCs and their neuronal derivatives for selecting substances with the neuroprotective activity using two classes of compounds - melanocortin family peptides and endocannabinoids. None of the tested compounds displayed cyto- or embryotoxicity. Both melanocortin peptides and endocannabinoids exerted neuroprotective effect in the neuronal precursors and IPSC-derived neurons subjected to hydrogen peroxide. The endocannabinoid N-docosahexaenoyl dopamine exhibited the highest neuroprotective effect (~70%) in the differentiated cultures enriched with dopaminergic neurons; the effect of melanocortin Semax was ~40%. The possibility of using other IPSC derivatives for selecting compounds with the neuroprotective activity is discussed.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células Cultivadas , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Endocanabinoides/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Melanocortinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos
11.
Biomed Khim ; 65(3): 180-201, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258142

RESUMO

New data on peptide drugs have been summarized; their high stability is due to both the introduction of Pro-Gly-Pro in various amino acid sequences and the modification of the glyproline fragment itself. Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 were used as proline-containing peptides. Tritiated peptides were obtained: Pro-Gly-Pro-Leu with specific radioactivity of 135 Ci/mmol, ACTH(6-9)Pro-Gly-Pro - 26 Ci/mmol, 5-oxo-Pro-Arg-Pro - 60 Ci/mmol and 5-oxo-Pro-His-Pro-NH2 - 75 Ci/mmol. The concentration of Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 in the blood was found to be about 200 times more than in the brain for intranasal administration, and in average 600 times more for intravenous administration. The stability of proline-containing peptides in vitro experiments was determined using different commercially available peptidases (leucine aminopeptidases, dipeptidases, carboxypeptidases B and Y), and using nasal mucus, microsomal fraction of the rat brain (IMPC) and rat blood plasma. During peptidase hydrolysis of Pro-Gly-Pro-Leu, the main metabolites were Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly. For ACTH(6-9)Pro-Gly-Pro, the main metabolites were Phe-Arg-Trp-Pro-Gly-Pro and Trp-Pro-Gly-Pro. In peptidase hydrolysis of 5-oxo-Pro-His-Pro-NH2, the major metabolite was 5-oxo-Pro-His-Pro. It was shown that with different methods of peptides administration the composition of the metabolites formed is different. Based on the data obtained, resistance to enzymatic cleavage of peptides and their metabolic pathways were evaluated. Thus, these new data have shown that the above approaches can be used to prolong the action of glyprolines in living objects. In this case, the degradation of proline-containing peptides occurs mainly not due to the action of proteases, but due to other ways of degradation. In general, the data presented in the review indicate the promise of intranasal way of introducing biologically active peptides into the brain of living organisms.


Assuntos
Peptídeos/química , Prolina/química , Sequência de Aminoácidos , Animais , Peptídeo Hidrolases/química , Estabilidade Proteica , Ratos
12.
Bull Exp Biol Med ; 167(2): 226-228, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236882

RESUMO

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 µg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.


Assuntos
Colo/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Oligopeptídeos/uso terapêutico , Restrição Física/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
13.
Bull Exp Biol Med ; 167(2): 293-296, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31243679

RESUMO

We studied the effects of Selank on morphological parameters of the liver in Wistar male rats subjected to chronic foot-shock stress. Selank was injected intraperitoneally in doses of 100, 300 and 1000 µg/kg 15 min before each stress session. Morphological and morphometrical analysis showed that chronic foot-shock stress induced hydropic degeneration of hepatocytes, an increase of the nucleus/cytoplasm ratio due to an increase in the area of nuclei and reduction of the cytoplasm area, the appearance of focal necroses, and lymphohistiocyte infiltration. Injection of Selank in all doses reduced the intensity of stress-induced degenerative changes. Administration of Selank in doses of 300 and 1000 µg/kg restored the nucleus/cytoplasm ratio in hepatocytes. The maximum stress-limiting effect was attained after administration of 300 µg/kg Selank.


Assuntos
Fígado/metabolismo , Oligopeptídeos/uso terapêutico , Estresse Fisiológico/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Eletrochoque , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
14.
Bull Exp Biol Med ; 166(6): 754-758, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028579

RESUMO

We studied immunocorrecting effects of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the model of "social" stress caused by sensory contact and intermale confrontation. Functional activity of the immune system of laboratory animals was evaluated in standard immunopharmacological tests: delayed-type hypersensitivity reaction, direct agglutination test, latex test for studying phagocytic activity of peripheral blood neutrophils, changes in differential leukocyte count, and weight of immunocompetent organs. It was found that changes in the immune response caused by "social" stress are multidirectional, which confirms the theory of stress-induced "immune imbalance". Semax acted as effective immune corrector restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrophils. This attested to the presence of immunomodulating properties in Semax and necessitates further studies in this field.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Fragmentos de Peptídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Hormônio Adrenocorticotrópico/farmacologia , Agressão , Animais , Animais não Endogâmicos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Imunidade Inata/efeitos dos fármacos , Testes de Fixação do Látex , Contagem de Leucócitos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia
15.
Dokl Biochem Biophys ; 479(1): 59-61, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29779096

RESUMO

A comparative study of the influence of regulatory proline peptides Pro-Gly-Pro, Pro-Arg-Pro, Pro-Gly-Pro-Leu, and Arg-Pro-Gly-Pro on the state of the hemostasis system was carried out in an experiment on male rats with metabolic syndrome. Under these conditions, repeated (7-fold) intranasal administration of the peptides in a daily dose of 50 µg/kg resulted in an increase in the anticoagulant potential of the blood, namely, in an increase in the anticoagulant, fibrinolytic, and antiplatelet activity 20 h and 7 days after the last peptide injection. The arginine-containing peptide Arg-Pro-Gly-Pro had the most pronounced and stable effect on haemostasis under these experimental conditions.


Assuntos
Hemostasia , Síndrome Metabólica/metabolismo , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Prolina , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Masculino , Síndrome Metabólica/sangue , Ratos , Ratos Wistar
16.
Biomed Khim ; 63(6): 546-552, 2017 Nov.
Artigo em Russo | MEDLINE | ID: mdl-29251617

RESUMO

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.


Assuntos
Fibrinolíticos/farmacologia , Hipolipemiantes/farmacologia , Peptídeos/farmacologia , Animais , Lipídeos/sangue , Prolina , Ratos
17.
Bull Exp Biol Med ; 163(6): 731-736, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29063333

RESUMO

We studied the effects of peptide drugs (HLDF-6, PGP, RPGP, and PGLP) and peptide pharmaceutical products (Semax, Selank, and thyroliberin) on proliferation and survival of mouse embryonic stem cells and their derivatives. Differentiation of mouse embryonic stem cells into neuronal precursors was evaluated. PGP and PGLP in concentrations of 10 and 0.1 µM, respectively, had little, but significant inhibitory effect on proliferative activity of cells. These peptides in concentrations of 10 and 0.1 µM, respectively, and Semax (10 and 0.1 µM) significantly increased the survival rate of mouse embryonic stem cells (serum deprivation). Moreover, study peptides had little effect on the formation of neuronal precursors from mouse embryonic stem cells. HLDF-6, Selank, and thyroliberin produced an insignificant effect on the differentiation of these cells into mature neurons. Analysis of differentiation of embryonic stem cells into GABA+ neurons showed that Selank, thyroliberin (100 µM), and NGF (100 ng/ml) decrease the ratio of these cells by 61, 58, and 87%, respectively, in comparison with the control. Our results indicate that these peptide compounds do not produce toxic effect during the embryonic and fetal period of life.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Hormônio Adrenocorticotrópico/análogos & derivados , Hormônio Adrenocorticotrópico/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Proteínas de Membrana/farmacologia , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Fator de Crescimento Neural/farmacologia , Neurônios/citologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Prolina/análogos & derivados , Prolina/farmacologia , Proteínas Recombinantes/farmacologia , Hormônio Liberador de Tireotropina/farmacologia
19.
Bull Exp Biol Med ; 163(4): 415-418, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28853100

RESUMO

We studied the effect of Selank administered intraperitoneally in doses of 100, 300, and 1000 µg/kg to male Wistar rats 15 min prior to restraint stress on the content of aminotransferases and total protein concentration in blood serum and intensity of free radical oxidation in the liver. Under conditions of acute restraint stress, Selank in doses of 100 and 300 µg/kg decreased catalase and superoxide dismutase activities and malondialdehyde concentration and increased total antioxidant activity in the liver homogenate. Administration of Selank in a dose of 1000 µg/kg reduced the content of aminotransferases in blood serum, decreased superoxide dismutase activity in the liver, and increased total antioxidant activity. Under conditions of chronic stress, Selank in all doses produced similar effects: reduced superoxide dismutase activity and malondialdehyde concentration in the liver tissue and AST activity in the serum. The other parameters remained unchanged.


Assuntos
Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/metabolismo , Oligopeptídeos/farmacologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Transaminases/metabolismo
20.
Dokl Biol Sci ; 474(1): 106-109, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28702721

RESUMO

Parkinson's disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals. At the same time, Selank decreased level of anxiety of rats with toxic damage of DA neurons in elevated cross shaped maze. Previously such effects of Selank were revealed in healthy rodents (rats and mice) with different models of psycho-emotional stress. Therefore, toxic damage of substantia nigra does not affect the response of the rat organism on this peptide.


Assuntos
Doença de Parkinson/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Hormônio Adrenocorticotrópico/análogos & derivados , Hormônio Adrenocorticotrópico/uso terapêutico , Animais , Ansiedade/tratamento farmacológico , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Masculino , Oligopeptídeos/uso terapêutico , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Transtornos Parkinsonianos/induzido quimicamente , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Ratos
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