Urinary biomarkers of oxidative status in a clinical model of oxidative assault.
BACKGROUND
We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans.


METHODS
The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and 24 hours (T24) after i.v. administration of treatment. Measurements included allantoin and the isoprostanes iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso-iPF(2alpha)-VI along with the prostaglandin 2,3-dinor-iPF(2alpha)-III, a metabolite of iPF(2alpha)-III. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry.


RESULTS
In all subjects, the levels of the biomarkers increased at T1: allantoin by 22% (P = 0.06), iPF(2alpha)-III by 62% (P < 0.05), iPF(2alpha)-VI by 41% (P < 0.05), 8,12-iso-iPF(2alpha)-VI by 58% (P < 0.05), and 2,3-dinor-iPF(2alpha)-III by 52% (P < 0.05). At T24, the F2-isoprostanes returned to their baseline levels; the levels of allantoin continued to increase, although the T24-T0 difference was not statistically significant.


CONCLUSIONS
These results indicate that urinary F2-isoprostanes are valid biomarkers and allantoin is a promising biomarker of oxidative status in humans.


CONCLUSIONS
The levels of biomarkers change quickly in response to oxidative assault and can be used to monitor oxidative status in humans in response to treatments related either to generation of free radicals (chemotherapy and radiation therapy) or to antioxidants (inborn metabolic diseases and Down syndrome).
Il'yasova
Dora
D
Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710, USA. dora.ilyasova@duke.edu
Spasojevic
Ivan
I
Wang
Frances
F
Tolun
Adviye A
AA
Base
Karel
K
Young
Sarah P
SP
Marcom
P Kelly
PK
Marks
Jeffrey
J
Mixon
Gabriel
G
DiGiulio
Richard
R
Millington
David S
DS
D000293:Adolescent; D000328:Adult; D000481:Allantoin / Q000652:urine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000652:urine*; D002853:Chromatography, Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D028441:F2-Isoprostanes / Q000652:urine*; D005260:Female; D005609:Free Radicals / Q000652:urine; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D018384:Oxidative Stress; D055815:Young Adult
D014408:Biomarkers, Tumor; D028441:F2-Isoprostanes; D005609:Free Radicals; D000481:Allantoin; D004317:Doxorubicin; D003520:Cyclophosphamide