δ-Aminolevulinate dehydratase activity and oxidative stress during melphalan and cyclophosphamide–BCNU–etoposide (CBV) conditioning regimens in autologous bone marrow transplantation patients

Departamento de Análises Clínicas e Toxicológicas, CCS, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
Pharmacological Research (Impact Factor: 4.41). 04/2009; 59(4):279-284. DOI: 10.1016/j.phrs.2008.12.005


Severe toxicity is associated with cytotoxic drugs used during the conditioning regimen (CR) preceding bone marrow transplantation (BMT). The aim of this study was to evaluate the involvement of oxidative stress and possible use of δ-aminolevulinate dehydratase (δ-ALA-D) activity as a marker of oxidative stress in autologous BMT patients. We have also compared common drugs that are used during CR, namely, melphalan (M-200) and cyclophosphamide–BCNU–etoposide (CBV), in order to determine whether either of them could be less toxic to patients in terms of oxidative stress. The sample consisted of 10 patients admitted for autologous BMT, 5 with M-200 CR and 5 with CBV CR and 10 healthy controls. Lipid peroxidation (estimated as thiobarbituric acid-reactive substances, TBARS), vitamin C, thiol levels, catalase, superoxide dismutase and δ-ALA-D activity were determined before CR, during CR and on days 10 and 20 after BMT. Signs of exacerbated oxidative stress were minimal before CR, except for the CVB group (patients with lymphoma) where an increase in TBARS and a decrease in P-SH were detected. Indices of oxidative stress changed in both groups (CBV and M-200) during CR and up to 20 days after BMT. There was a decrease in enzymatic and non-enzymatic antioxidant defenses and in δ-ALA-D activity and an increase in lipoperoxidation in the blood of both patient groups. In conclusion, CBV and, principally, M-200 caused oxidative stress in patients undergoing autologous BMT and blood δ-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.

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    • "It condenses two molecules of ␦aminolevulinic acid to produce porphobiliongen [16]. ␦-ALA-D is a thiol-containing enzyme, and its catalytic activity is very sensitive to oxidizing agents [17] [18] [19] and to situations associated with oxidative stress, including diabetes [20] [21], cancer [22] [23] [24] [25] and hemodialysis [26] [27]. Of toxicological significance, literature data have indicated that aminolevulinic acid, the substrate of ␦-ALA-D, exhibits pro-oxidant activity under significant physiological conditions [28] [29] [30] [31] [32] (Fig. 1). "
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