ABSTRACT
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.
Subject(s)
Gamma Rays , Glycerol/pharmacology , Hyperlipidemias/blood , Kidney/drug effects , Liver/drug effects , Surface-Active Agents/pharmacology , Alanine Transaminase/blood , Alanine Transaminase/drug effects , Alanine Transaminase/radiation effects , Animals , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/drug effects , Aspartate Aminotransferases/radiation effects , Bone Marrow Cells/drug effects , Bone Marrow Cells/radiation effects , Cholesterol/blood , Cholesterol/radiation effects , Creatinine/blood , Creatinine/radiation effects , Gamma Rays/adverse effects , Glutathione/drug effects , Glutathione/metabolism , Glutathione/radiation effects , Glycerol/analogs & derivatives , Glycerol/therapeutic use , Hyperlipidemias/drug therapy , Kidney/metabolism , Kidney/radiation effects , Liver/metabolism , Liver/radiation effects , Male , Mice , Micronuclei, Chromosome-Defective/drug effects , Micronuclei, Chromosome-Defective/metabolism , Micronuclei, Chromosome-Defective/radiation effects , Rats , Rats, Wistar , Surface-Active Agents/therapeutic use , Triglycerides/blood , Triglycerides/radiation effects , Tumor Cells, Cultured , Urea/blood , Urea/radiation effectsABSTRACT
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.
