Ethyl ferulate, a component with anti-inflammatory properties for emulsion-based creams.

Ethyl ferulate (FAEE) has been widely studied due to its beneficial heath properties and, when incorporated in creams, shows a high sun protection capacity. Here we aimed to compare FAEE and its precursor, ferulic acid (FA), as free radical scavengers, inhibitors of oxidants produced by leukocytes and the alterations in rheological properties when incorporated in emulsion based creams. The cell-free antiradical capacity of FAEE was decreased compared to FA. However, FAEE was more effective regarding the scavenging of reactive oxygen species produced by activated leukocytes. Stress and frequency sweep tests showed that the formulations are more elastic than viscous. The viscoelastic features of the formulations were confirmed in the creep and recovery assay and showed that the FAEE formulation was less susceptive to deformation. Liberation experiments showed that the rate of FAEE release from the emulsion was slower compared to FA. In conclusion, FAEE is more effective than FA as a potential inhibitor of oxidative damage produced by oxidants generated by leukocytes. The rheological alterations caused by the addition of FAEE are indicative of lower spreadability, which could be useful for formulations used in restricted areas of the skin.

Ascorbic acid potentiates the cytotoxicity of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin.

The interaction of ascorbic acid with 5-methoxy-3,4-dehydroxanthomegnin, an 1,4-naphthoquinone, was investigated using the cytotoxic index for McCoy cells by neutral red assay. The synergistic effect was observed when such compounds were added simultaneously, most probably due to hydrogen peroxide being generated by ascorbate-driven 5-methoxy-3,4-dehydroxanthomegnin redox cycling. Incubation of cells in the presence of 5-methoxy-3,4-dehydroxanthomegnin/ascorbic acid/catalase, an enzyme that destroys H2O2, resulted in an increase of cell survival, reinforcing the involvement of hydrogen peroxide generated as an important oxidizing agent that kills McCoy cells.

Assessment of monocytic component in acute myelomonocytic and monocytic/monoblastic leukemias by a chemiluminescent assay.

INTRODUCTION: Classically, the monocytic component of acute myelomonocytic (FAB-M4) and acute monocytic/monoblastic (FAB-M5) leukemias is demonstrated by nonspecific esterase positivity in cytochemical stainings. We have previously demonstrated that non-specific esterases from normal monocytes can be determined by a chemiluminescent method. In the present study, we investigated whether this assay can also determine the monocytic component of FAB-M4 and FAB-M5 and distinguish these acute myeloid leukemia (AML) categories. MATERIALS AND METHODS: Bone marrow samples were obtained from 66 patients with AML (M0, two cases; M1, 12 cases; M2, 13 cases; M3, 10 cases; M4, 11 cases; M5, 12 cases; M6, two cases; M7, four cases). Cells were incubated with a standard reaction mixture and chemiluminescence was measured for 10 min. Two parameters were assessed, the peak (PLE) and the integrated light emission (ILE). RESULTS: Both PLE and ILE were higher in FAB-M4 and FAB-M5 subtypes compared to other AML subtypes (P<0.001). In addition, the classification of AML cases into FAB-M4, FAB-M5 and nonmonocytic subtypes based on ILE analysis was concordant with alpha-naphthyl acetate esterase (ANAE) in 97% of cases (kappa coefficient 0.94, P<0.001). CONCLUSIONS: These findings indicate that this chemiluminescent assay was able to determine the monocytic component of FAB-M4 and FAB-M5 cells, and the classification of AML subtypes based on chemiluminescent analysis strongly agreed with the cytochemical ANAE-staining. In conclusion, this chemiluminescent assay is a simple, fast and objective method, which may be useful as an alternative tool in the differential diagnosis of AML subtypes.

Antibody-targeted horseradish peroxidase associated with indole-3-acetic acid induces apoptosis in vitro in hematological malignancies.

Indole-3-acetic acid (IAA), when oxidized by horseradish peroxidase (HRP), is transformed into cytotoxic molecules capable of inducing cell injury. The aim of this study was to test if, by targeting hematopoietic tumors with HRP-conjugated antibodies in association with IAA treatment, there is induction of apoptosis. We used two lineages of hematologic tumors: NB4, derived from acute promyelocytic leukemia (APL) and Granta-519 from mantle cell lymphoma (MCL). We also tested cells from 12 patients with acute myeloid leukemia (AML) and from 10 patients with chronic lymphocytic leukemia (CLL). HRP targeting was performed with anti-CD33 or anti-CD19 antibodies (depending on the origin of the cell), followed by incubation with goat anti-mouse antibody conjugated with HRP. Eight experimental groups were analyzed: control, HRP targeted, HRP targeted and incubated with 1, 5 and 10mM IAA, and cells not HRP targeted but incubated with 1, 5 and 10mM IAA. Apoptosis was analyzed by flow cytometry using annexin V-FITC and propidium iodide labeling. Results showed that apoptosis was dependent on the dose of IAA utilized, the duration of exposure to the prodrug and the origin of the neoplasia. Targeting HRP with antibodies was efficient in activating IAA and inducing apoptosis.

Inhibitory effect of gallic acid and its esters on 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH)-induced hemolysis and depletion of intracellular glutathione in erythrocytes.

The protective effect of gallic acid and its esters, methyl, propyl, and lauryl gallate, against 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH)-induced hemolysis and depletion of intracellular glutathione (GSH) in erythrocytes was studied. The inhibition of hemolysis was dose-dependent, and the esters were significantly more effective than gallic acid. Gallic acid and its esters were compared with regard to their reactivity to free radicals, using the DPPH and AAPH/pyranine free-cell assays, and no significant difference was obtained. Gallic acid and its esters not only failed to inhibit the depletion of intracellular GSH in erythrocytes induced by AAPH but exacerbated it. Similarly, the oxidation of GSH by AAPH or horseradish peroxidase/H(2)O(2) in cell-free systems was exacerbated by gallic acid or gallates. This property could be involved in the recent findings on pro-apoptotic and pro-oxidant activities of gallates in tumor cells. We provide evidence that lipophilicity and not only radical scavenger potency is an important factor regarding the efficiency of antihemolytic substances.