Avaliação do estresse oxidativo e da atividade da enzima d-aminolevulinato desidratase em pacientes transplantados de medula óssea

Abstract

Bone marrow transplantation (BMT) has been used in the treatment of a number of diseases. Before BMT, patients are submitted to a conditioning regime (CR) that consists of administration of high doses of chemo- or radiotherapy. This CR has the objective of eradicating the residual disease and inducing an immunosuppression that will allow the engraftment of cells infused in the BMT. The action of the cytostatic drugs, of radiotherapy and of the BMT itself is associated with the production of a great quantity of reactive oxygen species (ROS), which, if anti-oxidant defenses are inadequate, can lead to oxidative stress, which in turn has been implied in the etiology of several diseases and post-BMT complications. The objectives of this study were: to evaluate the oxidative status and to analyze aminolevulinic acid dehydratase activity (d-ALA-D) as a possible marker of oxidative stress in allogeneic or autologous BMT patients and compare these two modalities of BMT; to compare different CRs to determine which is less toxic in terms of oxidative stress; and to analyze d-ALA-D in the different CRs. In order to achieve these objectives, some indicators of oxidative stress, such as thiobarbituric acid reactive species (TBARS), vitamin C, catalase, superoxide dismutase, protein thiol groups (P-SH), non-protein thiol groups (NP-SH) and d- ALA-D, were evaluated in patients undergoing BMT at the University Hospital of the Universidade Federal de Santa Maria, between March 2007 and March 2008. The results obtained showed that patients presented signs of oxidative stress before BMT, during the CR and up to 20 days after BMT. A decrease in antioxidant defenses and in d-ALA-D activity was verified and an increase in lipid peroxidation in the blood of allogeneic and autologous patients was observed. In addition, there was a decrease in enzymatic and non-enzymatic antioxidants and in d-ALA-D activity in all CRs analyzed (fludarabine + cyclophosphamide FluCy, busulfan + cyclophosphamide BuCy and cyclophosphamide + total body irradiation CyTBI, for allogeneic patients and cyclophosphamide + BCNU+ etoposide CBV and melphalan, for autologous patients). There was also an increase in lipid peroxidation in the blood in all CRs, however, it was more pronounced with the use of CyTBI in allogeneic patients and with melphalan in autologous patients. In conclusion, this study demonstrated oxidative stress in allogeneic and autologous BMT patients. All CRs analyzed brought about an elevation of oxidative stress, however, this increase was greater with CyTBI (allogeneic patients) and melphalan (autologous patients). Finally, evaluation of d-ALA-D seems to be an efficient biomarker of oxidative stress in BMT patients, as well as to be reduced in these patients, also showed a negative correlation with the levels of TBARS and positive with antioxidants