Oxidation of glutathione peroxidase–deficient red cells by organic peroxides

Abstract

malignancy at 5 years was 0.43 (95% CI 016-1.15) and was unchanged at 10 years.Our data allow some interesting considerations. The probability of developing an acute leukemia in patients who received chemotherapy or radiotherapy for a previous malignancy (PM), including acute leukemia, is a well-known occurrence: secondary forms constitute approximately 8% to 10% of all acute leukemias and are usually myeloid. 6 The main reason for this event is that several drugs employed in the treatment of the PM, particularly topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines), and combined chemotherapy including alkylating agents, are considered potentially mutagenic. As suggested by Latagliata et al, 1 the use of intensive chemotherapy to cure APL, with the inclusion of topoisomerase II inhibitors, has a potential role in inducing a tMDS-AML. 7 In our cohort of patients, the number of secondary malignancies is lower than expected in the normal population. The estimated cumulative incidence at 5 and 10 years is also lower than that expected. Furthermore, the brief latency between the onset of the 2 malignancies leads to the hypothesis that the second malignancy is probably not related to the carcinogenic action of the drugs employed for the treatment of APL, but perhaps to a chance association only.These considerations suggest that APL treatment is not relevant in inducing the onset of secondary nonhematological malignancies. On the contrary, the action of topoisomerase II inhibitors, which represent one of the main anticancer drugs used in APL, could favor the development of a tMDS-AML with a leukemogenic action on blood stem cells.

Hydroxyurea-Induced Expression of Glutathione Peroxidase 1 in Red Blood Cells of Individuals with Sickle Cell Anemia

“…GPx1 has been suggested to be a minor antioxidant in RBCs on the basis of the findings that RBCs of mice lacking GPx1 appear normal unless stressed with lipid hydroperoxide and that the primary physiologic substrate of GPx1 in these cells is lipid hydroperoxide rather than H 2 O 2 (14,19). However, humans with deficient RBC GPx1 activity have been reported to demonstrate hemolysis (47), suggesting that GPx1 might be more important in human RBCs.…”

“…Given that the primary physiologic substrate of GPx1 in RBCs is lipid hydroperoxide (19), membrane oxidation would be expected to be increased in the RBCs of individuals with a low GPx1 activity. In addition, among the antioxidant enzymes, only GPx1 showed significant increase in HU(þ) compared with HU(-).…”

“…Deficiency of GPx1 renders human RBCs susceptible to oxidant stress (47). The primary physiologic substrate of GPx1 in RBCs is lipid hydroperoxide (19). GPx1 is susceptible to irreversible inactivation by its own substrates, likely as a consequence of the irreversible conversion of the active-site selenocysteine residue to dehydroalanine (DHA) (6).…”

The role of erythrocyte peroxiredoxin in detoxifying peroxides and in stimulating potassium efflux via the Gardos channels

“…1 The diagnostic criteria of the disorder have been presented elsewhere. 2 The condition is characterized by low incidence of infections, usually benign outcome, female predominance, and an HLA class II genetic predisposition.…”

“…1 The authors extended the discussion to include another family of peroxide detoxifying enzymes, the peroxiredoxins. Far from being restricted to micro-organisms, as implied by Johnson et al, peroxiredoxin family members are widely spread throughout mammalian tissues, including erythrocytes and macrophages.…”