Modulation of radiation-induced organs toxicity by cremophor-el in experimental animals.
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.
Ramadan
L A
LA
National Center for Radiation Research and Technology, (NCRRT), Drug Radiation Research Department, Atomic Energy Authority, P.O. Box 29, Cairo, Egypt. laila-ramadan@hotmail.com
Shouman
S A
SA
Sayed-Ahmed
M M
MM
El-Habit
O H
OH
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D002784:Cholesterol / Q000097:blood / Q000528:radiation effects; D003404:Creatinine / Q000097:blood / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014508:Urea / Q000097:blood / Q000528:radiation effects
D013501:Surface-Active Agents; D014280:Triglycerides; C000515:cremophor EL; D014508:Urea; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D005990:Glycerol