Chronic oxidative stress as a mechanism for radiation nephropathy.
Suppression of the renin-angiotensin system has proven efficacy for mitigation and treatment of radiation nephropathy, and it has been hypothesized that this efficacy is due to suppression of radiation-induced chronic oxidative stress. It is known that radiation exposure leads to acute oxidative stress, but direct evidence for radiation-induced chronic renal oxidative stress is sparse. We looked for evidence of oxidative stress after total-body irradiation in a rat model, focusing on the period before there is physiologically significant renal damage. No statistically significant increase in urinary 8-isoprostane (a marker of lipid peroxidation) or carbonylated proteins (a marker of protein oxidation) was found over the first 42 days after irradiation, while a small but statistically significant increase in urinary 8-hydroxydeoxy-guanosine (a marker of DNA oxidation) was detected at 35-55 days. When we examined renal tissue from these animals, we found no significant increase in either DNA or protein oxidation products over the first 89 days after irradiation. Using five different standard methods for detecting oxidative stress in vivo, we found no definitive evidence for radiation-induced renal chronic oxidative stress. If chronic oxidative stress is part of the pathogenesis of radiation nephropathy, it does not leave widespread or easily detectable evidence behind.
Lenarczyk
Marek
M
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Cohen
Eric P
EP
Fish
Brian L
BL
Irving
Amy A
AA
Sharma
Mukut
M
Driscoll
Collin D
CD
Moulder
John E
JE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001806:Blood Urea Nitrogen; D016026:Bone Marrow Transplantation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress; D051381:Rats; D014916:Whole-Body Irradiation / Q000009:adverse effects*
C075750:8-epi-prostaglandin F2alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine