Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration.
We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and alpha- and gamma-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt). In all subjects, PPCC and MDA levels did not change. erGSHt levels increased at T24 by 8% (p=0.03). Levels of alpha, gamma, and total tocopherols progressively decreased by 7%-15% (p <0.05). In subjects with low erGSHt levels (below median), PPCC mean levels progressively increased from 0.35 (T0) to 0.56 (T1) and 0.72 nmol carbonyl/mg protein (T24) (p =0.2). These results indicate that (1) plasma MDA is not a sensitive biomarker in humans; (2) PPCC potentially may be used, if antioxidant reserves are taken into account; (3) antioxidant reserves play an important role in the reaction to oxidative stress.
Il'yasova
Dora
D
Duke Comprehensive Cancer Center, Durham, NC 27710, USA. dora.ilyasova@duke.edu
Mixon
Gabriel
G
Wang
Frances
F
Marcom
P Kelly
PK
Marks
Jeffrey
J
Spasojevich
Ivan
I
Craft
Neal
N
Arredondo
Francisco
F
DiGiulio
Richard
R
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D016877:Oxidants / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects
D000970:Antineoplastic Agents; D015415:Biomarkers; D016877:Oxidants; D004317:Doxorubicin