title: Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration.
abstract: 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.
authors.affiliation: Duke Comprehensive Cancer Center, Durham, NC 27710, USA. dora.ilyasova@duke.edu
authors.forename: Dora
authors.initials: D
authors.lastname: Il'yasova
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mixon
authors.forename: Frances
authors.initials: F
authors.lastname: Wang
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Marks
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevich
authors.forename: Neal
authors.initials: N
authors.lastname: Craft
authors.forename: Francisco
authors.initials: F
authors.lastname: Arredondo
authors.forename: Richard
authors.initials: R
authors.lastname: DiGiulio
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016877:Oxidants; D004317:Doxorubicin