| Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes. | |
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MedLine Citation:
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PMID: 18353769 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sudheer K Mantena; M K Unnikrishnan; P Uma Devi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-18 |
Journal Detail:
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Title: Mutagenesis Volume: 23 ISSN: 1464-3804 ISO Abbreviation: Mutagenesis Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-30 Completed Date: 2008-09-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8707812 Medline TA: Mutagenesis Country: England |
Other Details:
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Languages: eng Pagination: 285-92 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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