title: In vivo radioprotection by 5-aminosalicylic acid.
abstract: The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7x10(9)M(-1)s(-1). The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Manipal 576119, India. sushdheer@yahoo.com
authors.forename: S K
authors.initials: SK
authors.lastname: Mantena
authors.forename: M K
authors.initials: MK
authors.lastname: Unnikrishnan
authors.forename: Ravi
authors.initials: R
authors.lastname: Joshi
authors.forename: V
authors.initials: V
authors.lastname: Radha
authors.forename: P Uma
authors.initials: PU
authors.lastname: Devi
authors.forename: T
authors.initials: T
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D002474:Cell-Free System; D002869:Chromosome Aberrations; D005720:Gamma Rays; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D019804:Mesalamine