RESUMEN
Pharmacological and cytogenetic evaluations of the protective effects of polyethoxylated castor oil cremophor-EL (cremophor) against hepato, renal and bone marrow toxicity induced by gamma irradiation in normal rats were carried out. A single dose of irradiation (6 Gy) caused hepatic and renal damage manifested biochemically as an elevation in levels of serum alanine and aspartate aminotransferase as well as an increase in blood urea. Cremophor administration at a dose level of 50 microl kg-1 intravenously 1 day before exposure to irradiation (6 Gy) protected the liver and kidney as indicated by the recovery of levels of hepatic aminotransferase, urea and lipid profiles to normal values. Gamma irradiation of male rats caused a decrease in reduced glutathione and an increase in the oxidized form in rat-liver homogenate. A highly significant increase in the incidence of micronucleated normochromatic erythrocytes and micronucleated polychromatic erythrocytes was observed after irradiation exposure. The induced genotoxicity in the bone marrow cells was corrected by pretreatment with cremophor. The findings of this study suggest that cremophor pretreatment can potentially be used clinically to prevent irradiation-induced hepato, renal and bone marrow toxicity without interference with its cytotoxic activity.
Asunto(s)
Rayos gamma , Glicerol/farmacología , Hiperlipidemias/sangre , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Tensoactivos/farmacología , Alanina Transaminasa/sangre , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/efectos de la radiación , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/efectos de la radiación , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/efectos de la radiación , Colesterol/sangre , Colesterol/efectos de la radiación , Creatinina/sangre , Creatinina/efectos de la radiación , Rayos gamma/efectos adversos , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Glutatión/efectos de la radiación , Glicerol/análogos & derivados , Glicerol/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Riñón/metabolismo , Riñón/efectos de la radiación , Hígado/metabolismo , Hígado/efectos de la radiación , Masculino , Ratones , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Micronúcleos con Defecto Cromosómico/metabolismo , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Ratas , Ratas Wistar , Tensoactivos/uso terapéutico , Triglicéridos/sangre , Triglicéridos/efectos de la radiación , Células Tumorales Cultivadas , Urea/sangre , Urea/efectos de la radiaciónRESUMEN
Accidental radiation exposure raises concern for functional modifications in the uterine physiology. In the current work, total body gamma-irradiation (0.7, 1.4 and 2.1 Gy) of non-pregnant adult female albino rats increased significantly the frequency and amplitude of uterine contractions in vivo. Administration of Thiola (a sulfhydryl containing agent) in doses of 100 or 250 mg kg-1, pre-irradiation or Piroxicam (a potent prostaglandin inhibitor) in a dose of 2 mg kg-1, pre- or post-irradiation failed to normalize the changes induced by gamma-irradiation. However, administration of Diltiazem (a Ca2+ channel blocker, 8 mg kg-1) pre- or post-irradiation caused a significant decrease in the frequency of uterine contractions (21% and 24% respectively) in comparison to the uterotonic pattern of gamma-irradiation alone. The results indicate a promising tocolytic activity of Diltiazem against the uterotonic effect of gamma-radiation.
