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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #193728

Title: PLASMA ANTIOXIDANTS IN SUBJECTS PRIOR TO HEMATOPOIETIC STEM CELL TRANSPLANTATION

Author
item WHITE, ALEXANDER - TUFTS-NEMC
item SOUSA, ANN MARIE - TUFTS-NEMC
item RYAN, HELEN - BAYSTATE MEDICAL CENTER
item Blumberg, Jeffrey
item FANBURG, BARRY - TUFTS-NEMC
item KAYYALI, USAMAH - TUFTS-NEMC

Submitted to: Review Article
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/10/2006
Publication Date: 10/1/2006
Citation: White, A.C., Sousa, A., Ryan, H.F., Blumberg, J.B., Fanburg, B.L., Kayyali, U.S. 2006. Plasma antioxidants in subjects prior to hematopoietic stem cell transplantation. Bone Marrow Transplantation. 38(7):513-520.

Interpretive Summary: ISUM-Plasma antioxidants in subjects prior to Hematopoietic Stem Cell Transplantation Oxidative damage to cells appears to contribute substantially to the aging process and risk for chronic disease. We employed a fortuitous clinical situation to examine the role of dietary antioxidants in conditions of high oxidative stress. Prior to undergoing Hematopoietic Stem Cell Transplantation (HSCT), patients appear compromised with skeletal and respiratory muscle weakness so we examined whether this condition was associated with reductions in dietary and cellular antioxidant defenses. Compared to healthy control subjects, we found lower plasma concentrations of the antioxidant enzyme glutathione peroxidase and higher levels of gamma-tocopherol in the HSCT group but no differences in alpha-tocopherol or malondialdehyde, a biomarker of lipid peroxidation. These observations extend further our understanding of antioxidants and oxidative stress during organ aging and may have direct clinical nutrition applications useful for preparing patients for the antioxidant-depleting chemo-irradiation therapies associated with HSCT.

Technical Abstract: Chemo-irradiation induced oxidative damage to vascular endothelium may contribute to pulmonary complications of hematopoietic stem cell transplantation (HSCT). We compared antioxidants, markers of oxidative stress and the ability of plasma to handle an oxidative stress in plasma or serum from 24 subjects prior to HSCT and 20 control subjects. The plasma concentration of extra cellular glutathione peroxidase (GPX-3) was significantly reduced in the HSCT subjects compared with controls (HSCT: 98 +/- 42 mg/ml, control: 169 +/- 56 mg/ml, p < 0.0001). The concentration of gamma - tocopherol was significantly higher in the HSCT subjects compared with controls (HSCT: 207 +/- 103 mg /dL; Control: 98 +/- 52 mg /dL ; p = 0.0002 ). The plasma concentrations of protein carbonyl, nitrotyrosine, malondialdehyde, alpha - tocopherol, Vitamin A, homocysteine, cysteine and cysteinylglycine did not differ between HSCT and control subjects. Plasma from HSCT subjects was as effective as control plasma in quenching menadione-induced intracellular ROS production in human microvascular endothelial cells. In summary, subjects prior to HSCT have significantly reduced plasma concentrations of GPx-3, elevated plasma gamma - tocopherol yet retain the ability to quench an acute oxidative stress. These changes may play a role in organ senescence and chronic oxidative stress in the HSCT population.