RESUMO
Pifithrin alpha (PFTalpha), one of the first known low molecular weight modulators of activity of tumor suppressor p53, increases survival of hemopoietic clonogenic cells (evaluated by the criterion of formation of endogenous spleen CFU-C8 colonies in irradiated animals). This effect appeared when PFTalpha was administered either before or after irradiation. Increase in CFU-C8 was also observed after administration of two PFTalpha analogs, derivatives of 2-amino-4,5,6,7-tetrahydrobenzothiazole. These included a parent compound, 2-ATBT (2-amino-4,5,6,7-tetrahydrobenzothiazole), which is used for synthesis of PFTalpha, and a product of its intramolecular cyclization under physiological conditions, cyclo-PFT (2-(4-methylphenyl)imidazo[2,1-b]-5,6,7,8-tetrahydrobenzothiazole). Earlier we found that many low molecular weight compounds increasing number of CFU-C8 (e.g. isothiourea derivatives) demonstrate NO inhibitory activity. Such activity was also found in 2-ATBT and cyclo-PFT by means of EPR spectroscopy of NO. These compounds caused more than twofold inhibition of NO production in vivo. Thus, it has been demonstrated that PFTalpha and its structural analogs increase survival of hemopoietic clonogenic cells in vivo, and NO may play a role in the mechanism of this effect.
Assuntos
Benzotiazóis/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Imidazóis/farmacologia , Óxido Nítrico/fisiologia , Protetores contra Radiação/farmacologia , Tolueno/análogos & derivados , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Benzotiazóis/síntese química , Benzotiazóis/química , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos da radiação , Imidazóis/síntese química , Imidazóis/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Óxido Nítrico/biossíntese , Protetores contra Radiação/síntese química , Protetores contra Radiação/química , Baço/citologia , Baço/efeitos dos fármacos , Baço/efeitos da radiação , Relação Estrutura-Atividade , Tolueno/síntese química , Tolueno/química , Tolueno/farmacologiaRESUMO
We studied the effects of systemic transplantation of mesenchymal stem cells obtained after culturing of autologous bone marrow on psychophysiological status of Wistar rats after diffuse brain trauma. Two months after systemic injection of mesenchymal stem cells we observed a decrease in manifestations of emotional behavioral reactions (anxiety and excitability) and shortening of the time of realization of drinking behavior in a T-maze. A significant positive effect of systemic transfusion of mesenchymal stem cells on avoidance conditioning in a shuttle box was observed 3 months after brain injury.
Assuntos
Lesões Encefálicas/psicologia , Lesões Encefálicas/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Ansiedade/fisiopatologia , Ansiedade/psicologia , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Lesões Encefálicas/fisiopatologia , Emoções/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos WistarRESUMO
Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic, angiogenic, and, presumably, neurotrophic effects. The therapeutic effect visually manifested on day 2 after intravenous injection of mesenchymal stem cells during the early period of reparative regeneration of ischemic cell and tissue structures of the brain. The neuroprotective effect of mesenchymal stem cells was more pronounced against the background of basic therapy.
Assuntos
Lesões Encefálicas/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Neurônios/citologia , Animais , Lesões Encefálicas/patologia , Proliferação de Células , Técnicas Histológicas , Injeções Intravenosas , Masculino , Neovascularização Fisiológica/fisiologia , Ratos , Ratos Wistar , Transplante Isogênico/métodosRESUMO
We studied the effect of NO synthase inhibitor 2-amino-5,6-dihydro-4H-1,3-thiazine (2-ADT) on the cardiovascular system in rats with endotoxic shock. Blood pressure, heart rate, and respiratory rate were recorded. E. coli lipopolysaccharide decreased blood pressure and heart rate. 2-ADT in a dose of 5 mg/kg normalized these hemodynamic parameters. The normalizing effect of 2-ADT decreased with increasing the dose of this preparation. 2-ADT in high doses (10, 20, and 30 mg/kg) and repeated injections of the preparation caused death of experimental animals.
Assuntos
Inibidores Enzimáticos/farmacologia , Hemodinâmica/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Respiração/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Tiazinas/farmacologia , Animais , Relação Dose-Resposta a Droga , Endotoxinas/toxicidade , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/toxicidade , Frequência Cardíaca/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Ratos , Ratos Wistar , Choque Séptico/fisiopatologia , Tiazinas/administração & dosagem , Tiazinas/toxicidadeRESUMO
Using the method of electron paramagnetic spectroscopy we demonstrated that thiazine-thiazoline compounds and aminoethyl isothiourea containing the thioamidine group inhibit NO production in the liver of endotoxin-treated mice. Injection of these agents to anesthetized rats increased arterial pressure and enhanced respiration rate. This effect probably reflects inhibition of not only inducible, but also the constitutive synthesis of NO by compounds with thioamidine group.
