Evaluation of oxidative and antioxidative parameters in pediatric hematopoietic SCT patients

Abstract

Conditioning regimens preceding hematopoietic SCT (HSCT) usually consist of high-dose chemotherapy. Chemotherapy and radiation therapy are associated with increased formation of free radicals and depletion of critical plasma and tissue antioxidants. Oxidative stress and antioxidant depletion have been described during the transplantation period in HSCT patients. In a limited number of studies, it was observed that the conditioning regimen resulted in oxidative stress and antioxidant depletion in HSCT patients. The objective of this study was to look for further evidence of oxidative stress and antioxidant status in pediatric HSCT patients. In this study, blood samples were collected from 21 pediatric allo-HSCT patients before and after conditioning therapy. Erythrocyte and plasma malondialdehyde (MDA) levels, erythrocyte reduced and oxidized glutathione (GSH) levels, erythrocyte antioxidant enzymes activities, plasma a-tocopherol and b-carotene levels were determined. After high-dose chemotherapy, erythrocyte and plasma MDA levels increased. Reduced GSH levels decreased whereas oxidized GSH levels increased first and then decreased significantly compared with the values before the chemotherapy regimen. It was also observed that catalase, superoxide dismutase and GSH-S-transferase activities decreased, but there was no change in GSH peroxidase activity. On the other hand, plasma a-tocopherol levels increased, but b-carotene levels did not change.

Oxidative Protein Damage with Carbonyl Levels and Nitrotyrosine Expression after Chemotherapy in Bone Marrow Transplantation Patients

“…It seems that the effect of donor neutrophils is not greater than the effect of chemotherapy. We demonstrated that a conditioning regimen results in oxidative stress and depletion of antioxidants in pediatric HSCT patients in our previous study [15]. The results of this study indicate chronic oxidative stress in the plasma and erythrocytes of the patients, which increased gradually over a period of 28 days following chemotherapy and HSCT thereafter.…”

Changes in Antioxidant Defense System Using Different Lipid Emulsions in Parenteral Nutrition in Children after Hematopoietic Stem Cell Transplantation

“…The role of oxidative stress (OS) is well known in the pathogenesis of acquired malnutrition [ 4 , 5 ]. Conditioning therapy given to HSCT recipients increases the production of reactive oxygen species and decreases the concentration of antioxidants and certain enzymes, vitamins E and C, and β-carotene [ 2 , 6 , 7 ]. This is probably responsible for the acute and delayed toxic effects that cytostatic drugs may have on tissues such as the gastrointestinal system, lungs, liver, or bladder [ 7 ].…”

Thioredoxin-1 confines T cell alloresponse and pathogenicity in graft-versus-host disease

“…Mechanistically, Trx1 reduced ROS accumulation in donor T cells and decreased Trx1 downstream molecules including NF-κB and T-bet, which restrained the ability of T cells to activate, expand, and migrate to the target organs in response to alloantigens in vivo. The contributions of preexisting disease conditions and the conditioning regimens increase cellular ROS, which correlates with elevated oxidative stress in all BMT recipients (8,9). Alloantigen-activated T cells exhibit higher cellular mitochondrial ROS generation and contain less antioxidant than their non-alloreactive counterparts (15).…”

“…Oxidative stress has been considered an unavoidable consequence of allo-HCT and may be an important factor in exacerbating GVHD (7). Owing to the contributions of preexisting disease conditions and the requirement for conditioning regimens that increase cellular reactive oxygen species (ROS), oxidative stress is elevated in all HCT recipients (8,9). Excess nitric oxide (NO) production was previously observed in both clinical GVHD (10,11) and experimental models (11,12).…”