RESUMEN
The investigations performed revealed that sulfhydryl compounds (reduced glutathione, cysteine and mesna) reduced the acute and subacute toxicity of 5-fluorouracil in mice. The above compounds changed pharmacokinetics of 5-fluorouracil increasing its accumulation in tissue compartment. The studies on 5-Fu distribution revealed its increased concentration in certain organs after administration of only certain sulfhydryl-containing compounds and only after certain doses.
Asunto(s)
Fluorouracilo/toxicidad , Compuestos de Sulfhidrilo/farmacología , Animales , Cisteína/farmacología , Fluorouracilo/metabolismo , Glutatión/farmacología , Cinética , Dosificación Letal Mediana , Masculino , Mesna/farmacología , Ratones , Ratas , Ratas EndogámicasRESUMEN
The influence of three chosen model sulfhydryl groups containing compounds, characterized by increasing size of molecule--cysteine, glutathione and insulin on antineoplastic activity of 5-fluorouracil (5-FU) and 6-mercaptopurine (6-MP) against murine leukemia L-1210 5-FU and 6-MP and murine sarcoma Sa 180, was studied. Sulfhydryl compounds failed to change in most cases the therapeutic (antineoplastic) effect of 5-FU and 6-MP. However, certain doses of these sulfhydryl compounds enhanced the cytostatic effect of 6-MP in respect to Sa-180.
Asunto(s)
Fluorouracilo/uso terapéutico , Mercaptopurina/uso terapéutico , Neoplasias Experimentales/tratamiento farmacológico , Compuestos de Sulfhidrilo/farmacología , Animales , Cisteína/farmacología , Sinergismo Farmacológico , Glutatión/farmacología , Insulina/farmacología , Leucemia L1210/tratamiento farmacológico , Ratones , Ratones Endogámicos DBA , Sarcoma 180/tratamiento farmacológicoRESUMEN
Investigations were carried out on spontanously hypertensive rats (SHR) of F3 and F4 generation of Okamoto-Aoki strain and on normotensive rats (NR) of Wistar strain. Blood pressure was measured by an indirect method. The haematological determinations were carried out using classical methods. The difference between SHR and normotensive rats were found not only in the values of blood pressure and in the number of erythrocytes but also in the number of leucocytes and the haemogram. The percentage of neutrocytes was significantly higher in 5 week-old female SHR than in NR of the some age and sex. The whole number of white cells depended on sex and age of animals but it was always lower in SHR than in NR. This seems to be independent of the changes in blood pressure.