Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes.
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.
Mantena
Sudheer K
SK
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka, India.
Unnikrishnan
M K
MK
Uma Devi
P
P
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002875:Chromosomes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005720:Gamma Rays; D008297:Male; D051379:Mice; D011837:Radiation-Protective Agents / Q000009:adverse effects / Q000494:pharmacology*; D012460:Sulfasalazine / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors
D011837:Radiation-Protective Agents; D012460:Sulfasalazine