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Arsenic has been proposed as a chemotherapeutic agent for leukemia and other solid tumors. However, its environmental exposure has been linked epidemiologically with an elevated carcinoma risk (i.e. skin, bladder and lung), with cellular oxidative stress being implicated in both induced-arsenic toxicity and carcinogenicity. Consequently, antioxidants may differentially interfere in these effects. The human mammary adenocarcinoma lines MCF-7 and ZR-75-1 were treated in vitro with 200 microM NaAsO(2) (As), 5 microM silymarin (S) and/or 50 microM quercetin (Q). The following biomembrane parameters were assessed: sialic acid (SA) in gangliosides, gamma-glutamyltranspeptidase activity (GGT), conjugated dienes and free radical activity, in order to evaluate the arsenite-flavonoid interactions. The time-dependent arsenite toxicity was not prevented by flavonoids in ZR-75-1 cells, whereas quercetin protected MCF-7 cells for 8 h. With regard to GGT, only quercetin protected ZR-75-1 cells against stress. In MCF-7 cells, the arsenite-induced GGT activity was not counteracted by either quercetin or silymarin. S, Q, As and As + S treatments reduced the SA content only in the MCF-7 membrane, while As + Q treatment increased it in both lines. The membrane resistance to lipid oxidation in these cells enclosed the up-regulation of GGT activity and sialylglycolipid content. Taking these results together, quercetin interfered with arsenite toxicity, whereas silymarin was not able. Thus, the potential role of flavonoids as co-adjutants may differ widely in therapeutic protocols.

Arsenic (As) is a worldwide immunotoxic agent that is in contaminated waters and consumed by mammals. Phytotherapy may counteract its harmful effects. Lantana grisebachii Stuck (LG, Verbenaceae) and its extract are proposed as protective, given vvits in vitro bioactivity. The aim was to determine the protective capacity of the aqueous LG extract on splenocytes exposed in vivo to arsenic. Splenocytes were obtained from an arsenicosis model (Wistar rats consuming orally 0 [control; C] or 5 mg/Kg/d of As) that received 0–100 mg/Kg/d of LG extract for 30 days. As content (total reflection X-ray fluorescence), fatty acid profile (gas chromatography), γ-glutamyl transpeptidase activity (Szasz method), peroxides (xylenol orange-based assay), and nitrites (Griess reaction) were then assayed in viable splenocytes. Data were analyzed with ANOVA and the Tukey's test (p <.05). It was observed that the splenocytes contained 2.2 mg/Kg of this elemental arsenic. With γ-glutamyl transpeptidase inhibition and consequent triggering of hydroperoxides (p <.05), it was observed to increase saturated fatty acids and alter lipid profiles. LG treatment avoided damaging effects with values similar to unexposed C (p <.05), and cellular arsenic concentration (p <.0001). In conclusion, the aqueous extract of L. grisebachii counteracted arsenic toxicity in rat splenocytes by preventing its cellular accumulation and induction of lipid and redox disturbances, which may impair immune function. [ABSTRACT FROM AUTHOR]

Since curcumin, a polyphenol extracted from the rhizomes of Curcuma longa L. (Zingiberaceae), has been proposed for breast cancer chemoprevention, the aim of the present work was to determine if it had anti-tumour effects on mammary cells which are resistant to oxidative damage. ZR-75-1 cells were treated with curcumin and copper(II) sulphate in order to evaluate cell death and γ-glutamyltranspeptidase (GGTP) activity. Curcumin was cytotoxic in a dosedependent manner (loss of viability with lactatedehydrogenase release) with apoptotic effects on ZR-75-1 cells. Also, curcumin displayed an antioxidant effect only on the copper-oxidized cells. The GGTP activity was decreased in a dose-dependent manner by curcumin, with the changes in this parameter accounting for neoplastic inhibition (direct relation between the enzyme activity and cellular viability). Summing up, our results suggest that curcumin induced apoptosis in ZR-75-1 with an antioxidant activity performed on those treated with copper(II) sulphate, which should be explored more thoroughly with the involvement of the GGTP enzyme activity as biomarker of their malignancy. [ABSTRACT FROM AUTHOR]