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 . ␦-ALA-D is a thiol-containing enzyme, and its catalytic activity is very sensitive to oxidizing agents    and to situations associated with oxidative stress, including diabetes  , cancer     and hemodialysis  . Of toxicological significance, literature data have indicated that aminolevulinic acid, the substrate of ␦-ALA-D, exhibits pro-oxidant activity under significant physiological conditions      (Fig. 1). "
[Show abstract][Hide abstract] ABSTRACT: Sepsis is a potentially deadly complication that can be caused by different factors. Actually, it is known that oxidative stress is involved in the pathogenesis of sepsis. Thus, the aim of this study was to evaluate the effect of diphenyl diselenide (PhSe)(2), an emergent compound, on oxidative stress parameters induced by sepsis in rats. Animals were pre-injected with (PhSe)(2) or vehicle. Twenty-four hours later, sepsis was induced by cecal ligation puncture (CLP). After 12 h, liver was taken for thiobarbituric acid reactive species (TBARS) measurement, δ-aminolevunic acid dehydratase (δ-ALA-D), Cu/Zn superoxide dismutase (Cu/Zn SOD) and catalase (CAT) activities assay. The sepsis increased TBARS, inhibited δ-ALA-D, activated Cu/Zn SOD and had a tendency to decrease CAT activity. However, (PhSe)(2) prevented the TBARS formation, but did not prevent the inhibition of δ-ALA-D activity in the animals with damage. Thus, this study showed that (PhSe)(2) partially prevents the oxidative stress induced by sepsis, indicating the potential of this compound as a treatment for this pathology. Nevertheless, more tests should be performed to confirm the hypothesis suggested here.
Full-text · Article · Aug 2011 · Pathology - Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Adriamycin is a potent antitumor drug that causes severe cardiotoxicity. However, the toxic mechanisms are not clear. We used a proteomics approach to analyze changes in protein profiles after adriamycin-induced changes in hemodynamic factors. Although adriamycin itself did not affect left ventricular developed pressure (LVDP) or left ventricular end diastolic pressure (LVEDP), the drug did enhance susceptibility to ischemia-reperfusion-induced changes in LVDP, LVEDP and heart rate. Adriamycin altered the expression of 52 proteins, primarily energy metabolism and cytoskeleton proteins. Adriamycin decreased the expression of the metabolism-related proteins, ATP synthase, Sdha protein, Triose phosphate isomerase 1 (TPI-1), pyruvate dehydrogenase E1 alpha1, 6-phosphofructokinase, and fructose-1,6-bisphosphatase, as did cytoskeletal proteins, such as actin. Alterations in energy metabolism and subsequent free radical production may affect cytoskeletal protein expression, producing adriamycin-induced changes in cardiac hemodynamics.
No preview · Article · Sep 2010 · Immunopharmacology and Immunotoxicology
[Show abstract][Hide abstract] ABSTRACT: Delta-aminolevulinate dehydratase (δ-ALA-D) enzyme is sensitive to pro-oxidant agents, including molecular oxygen. Here, we tested whether hyperoxygenation after total intravenous (i.v.) anesthesia could interact with the type of anesthesia (dexmedetomidine, continuous infusion; 0.5 μg/kg/h or remifentanil, continuous infusion; 0.3 μg/kg/min) plus propofol using blood δ-ALA-D activity and thiobarbituric acid reactive substances (TBARS) levels as ending points of toxicity. In absence or presence of dithiothreitol (DTT), δ-ALA-D activity was reduced after hyperoxygenation in the group treated with remifentanil and was not modified in dexmedetomidine group. TBARS increased considerably in the blood of both groups of patients after oxygenation. The results obtained here suggest that the hyperoxygenation was associated with a marked increase in TBARS production regardless of the type of anesthesia. δ-ALA-D activity was only inhibited in remifentanil group, which indicates a possible interaction between oxygenation and the type of anesthetic. This is the first demonstration that dexmedetomidine may protect blood δ-ALA-D from oxidation. However, further studies are necessary to establish a possible antioxidant role of dexmedetomidine against hyperoxygenation in human blood.
No preview · Article · Apr 2011 · Human & Experimental Toxicology