RESUMO
Anti-inflammatory effects of GB-115 compound (N-phenylhexanoyl-glycyl-L-tryptophan amide) injected intraperitoneally in doses of 0.1, 1, and 10 mg/kg were demonstrated on the model of ConA- and carrageenan-induced inflammation. Intraperitoneal injection of GB-115 in a dose of 1 mg/kg to C57Bl/6 female mice with experimental autoimmune encephalomyelitis significantly alleviated the pathological symptoms, improved spontaneous locomotor activity, promoted recovery of thymus weight, and reduced edema and neutrophil infiltration of the perivascular space of the brain tissue. Intraperitoneal injection of GB-115 in a dose of 1 mg/kg suppressed generation of active oxygen forms by neutrophils in the chemiluminescence test.
Assuntos
Anti-Inflamatórios/farmacologia , Colecistocinina/análogos & derivados , Dipeptídeos/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Carragenina/efeitos adversos , Carragenina/farmacologia , Colecistocinina/farmacologia , Concanavalina A/efeitos adversos , Concanavalina A/farmacologia , Feminino , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Timo/efeitos dos fármacosRESUMO
Preclinical safety investigations of newly synthesized dipeptide compound GB-115 (amide N-phenylhexanoyl-glycyl-L-tryptophan), an antagonist of cholecystokinin receptors, were performed. No animals were lost after GB-115 acute oral administration at a maximum dose of 6000 mg/kg in mice and at 3500 mg/kg in rats. GB-115 administered per os during 6 months in rabbits and rats (both males and females) at the doses of 0.1 and 10 mg/kg induced no irreversible pathological changes in organs and systems studied. The tested dipeptide exhibited no allergenic, immunotoxic and mutagenic activity, and did not affect generative function and the antenatal and postnatal development of progeny. GB-115 at a dose of 10 mg/kg produced suppression of the inflammatory reaction to concanavalin A.
Assuntos
Dipeptídeos/efeitos adversos , Dipeptídeos/farmacologia , Receptores da Colecistocinina/antagonistas & inibidores , Animais , Concanavalina A/efeitos adversos , Concanavalina A/farmacologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Cobaias , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Coelhos , RatosRESUMO
We studied the effects of a new dipeptide with anxiolytic activity (GB-115, N-phenylhexanoyl-glycyl-L-tryptophan amide) on parameters of the immune in intact mice and in animals with secondary immunodeficiency caused by cyclophosphamide. GB-115 in doses of 0.1-10 mg/kg stimulated phagocytic activity of peritoneal macrophages and humoral immune response in intact mice. GB-115 exhibited immunocorrecting activity in animals with secondary immunodeficiency.
Assuntos
Dipeptídeos/farmacologia , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Relação CD4-CD8 , Ciclofosfamida/toxicidade , Dipeptídeos/administração & dosagem , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/imunologia , Fatores Imunológicos/administração & dosagem , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Fagocitose/efeitos dos fármacosRESUMO
Study of polymorphism in 3 genes of the glutathione S-transferase family (GSTM1, GSTT1, and GSTP1) in children with Ehlers-Danlos syndrome whose cells were defective in repair of gamma-induced DNA damages revealed accumulation of GSTM1(+) genotypes compared to children of the control group. Generation of reactive oxygen species by neutrophils from patients with this syndrome was higher than in healthy donors. Our results indicate that glutathione S-transferase genes are involved in the resistance to mutagenic agents and demonstrate medical and genetic peculiarities of patients with Ehlers-Danlos syndrome.
Assuntos
Síndrome de Ehlers-Danlos/genética , Linfócitos/metabolismo , Mutagênicos/farmacologia , Polimorfismo Genético , Adolescente , Cloreto de Cádmio/farmacologia , Criança , Dano ao DNA , Resistência a Medicamentos , Síndrome de Ehlers-Danlos/sangue , Feminino , Raios gama , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Glutationa Transferase/genética , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Masculino , Espécies Reativas de Oxigênio/metabolismoRESUMO
Noopept, a peptide analog of piracetam, enhanced phagocytic activity of mouse peritoneal macrophages, stimulated humoral and cellular immune response to various antigens, and markedly increased spontaneous proliferative activity of splenocytes. In animals with secondary immune deficiency caused by cyclophosphamide, noopept exhibited immunocorrector properties.
