title: Radiation nephropathy is not mitigated by antagonists of oxidative stress.
abstract: Abstract Persistent, chronic oxidative injury may play a mechanistic role in late radiation injury. Thus antioxidants may be useful as mitigators of radiation injury. The antioxidants deferiprone, genistein and apocynin were tested in a rat radiation nephropathy model that uses single-fraction total-body irradiation (TBI) followed by syngeneic bone marrow transplant. Deferiprone was added to the drinking water at 1.0 or 2.5 g/liter, starting 3 days after the TBI. Urinary bleomycin-detectable iron, which could enhance production of oxygen radicals, was reduced in the rats on deferiprone compared to untreated rats, but deferiprone did not mitigate radiation nephropathy. Genistein added to the chow at 750 mg/kg starting immediately after TBI did not mitigate radiation nephropathy. Apocynin added to the drinking water at 250 mg/liter immediately after TBI did not mitigate radiation nephropathy. Thus three different types of antioxidants, when used at doses consistent with an antioxidant effect, had no mitigation efficacy against radiation nephropathy.
authors.affiliation: Departments of Medicine and, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Cohen
authors.forename: Brian L
authors.initials: BL
authors.lastname: Fish
authors.forename: Amy A
authors.initials: AA
authors.lastname: Irving
authors.forename: Mohan M
authors.initials: MM
authors.lastname: Rajapurkar
authors.forename: Sudhir V
authors.initials: SV
authors.lastname: Shah
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D051381:Rats; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D011837:Radiation-Protective Agents