Document Detail


Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes.
MedLine Citation:
PMID:  18353769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sulfasalazine (SAZ), a prescribed drug for inflammatory bowel disease, is a potent scavenger of reactive oxygen species. The present study was undertaken to ascertain its ability to protect against gamma radiation-induced damage. Acute toxicity of the drug was studied taking 24-h, 72-h and 30-day mortality after a single intraperitoneal injection of 400-1200 mg/kg body weight (b.wt.) of the drug. The drug LD(50) for 24- and 72-h/30-day survival were found to be 933 and 676 mg/kg b.wt., respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 30-180 mg/kg SAZ 30 min before gamma irradiation (RT) with 4 Gy produced a significant dose-dependent reduction in the RT-induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 120 mg/kg b.wt. At this dose, SAZ produced >60% reduction in the RT-induced percent aberrant metaphases and micronucleated erythrocytes. SAZ also produced a significant increase in the ratio of polychromatic erythrocytes to normochromatic erythrocytes from that of irradiated control. Injection of 120 mg/kg of the drug 60 or 30 min before or within 15 min after 4 Gy whole-body RT resulted in a significant decrease in the percent of aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h post-irradiation; the maximum effect was seen when the drug was administered 30 min before irradiation. These results show that SAZ protect mice against RT-induced chromosomal damage and cell cycle progression delay. SAZ also protected plasmid DNA (pGEM-7Zf) against Fenton's reactant-induced breaks, suggesting free radical scavenging as one of the possible mechanism for radiation protection.
Authors:
Sudheer K Mantena; M K Unnikrishnan; P Uma Devi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-18
Journal Detail:
Title:  Mutagenesis     Volume:  23     ISSN:  1464-3804     ISO Abbreviation:  Mutagenesis     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-30     Completed Date:  2008-09-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707812     Medline TA:  Mutagenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  285-92     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / drug effects*,  metabolism,  radiation effects
Chromosomes / drug effects*,  metabolism,  radiation effects*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Female
Gamma Rays
Male
Mice
Radiation-Protective Agents / adverse effects,  pharmacology*
Sulfasalazine / adverse effects,  pharmacology*
Time Factors
Chemical
Reg. No./Substance:
0/Radiation-Protective Agents; 599-79-1/Sulfasalazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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