RESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Colecistoquinina/análogos & derivados , Dipéptidos/farmacología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Carragenina/efectos adversos , Carragenina/farmacología , Colecistoquinina/farmacología , Concanavalina A/efectos adversos , Concanavalina A/farmacología , Femenino , Inflamación/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Timo/efectos de los fármacosRESUMEN
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.
Asunto(s)
Dipéptidos/efectos adversos , Dipéptidos/farmacología , Receptores de Colecistoquinina/antagonistas & inhibidores , Animales , Concanavalina A/efectos adversos , Concanavalina A/farmacología , Evaluación Preclínica de Medicamentos , Femenino , Cobayas , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ratones , Conejos , RatasRESUMEN
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.
Asunto(s)
Dipéptidos/farmacología , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Factores Inmunológicos/farmacología , Animales , Formación de Anticuerpos/efectos de los fármacos , Relación CD4-CD8 , Ciclofosfamida/toxicidad , Dipéptidos/administración & dosificación , Síndromes de Inmunodeficiencia/inducido químicamente , Síndromes de Inmunodeficiencia/inmunología , Factores Inmunológicos/administración & dosificación , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Fagocitosis/efectos de los fármacosRESUMEN
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.
Asunto(s)
Síndrome de Ehlers-Danlos/genética , Linfocitos/metabolismo , Mutágenos/farmacología , Polimorfismo Genético , Adolescente , Cloruro de Cadmio/farmacología , Niño , Daño del ADN , Resistencia a Medicamentos , Síndrome de Ehlers-Danlos/sangre , Femenino , Rayos gamma , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Glutatión Transferasa/genética , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Masculino , Especies Reactivas de Oxígeno/metabolismoRESUMEN
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.