Ascorbate (Asc) as a single agent suppressed growth of several tumor cell lines in a mouse model. It has been tested in a Phase I Clinical Trial on pancreatic cancer patients where it exhibited no toxicity to normal tissue yet was of only marginal efficacy. The mechanism of its anticancer effect was attributed to the production of tumoricidal hydrogen peroxide (H2O2) during ascorbate oxidation catalyzed by endogenous metalloproteins. The amount of H2O2 could be maximized with exogenous catalyst that has optimized properties for such function and is localized within tumor. Herein we studied 14 Mn porphyrins (MnPs) which differ vastly with regards to their redox properties, charge, size/bulkiness and lipophilicity. Such properties affect the in vitro and in vivo ability of MnPs (i) to catalyze ascorbate oxidation resulting in the production of H2O2; (ii) to subsequently employ H2O2 in the catalysis of signaling proteins oxidations affecting cellular survival pathways; and (iii) to accumulate at site(s) of interest. The metal-centered reduction potential of MnPs studied, E1/2 of MnIIIP/MnIIP redox couple, ranged from −200 to +350 mV vs NHE. Anionic and cationic, hydrophilic and lipophilic as well as short- and long-chained and bulky compounds were explored. Their ability to catalyze ascorbate oxidation, and in turn cytotoxic H2O2 production, was explored via spectrophotometric and electrochemical means. Bell-shape structure-activity relationship (SAR) was found between the initial rate for the catalysis of ascorbate oxidation, vo(Asc)ox and E1/2, identifying cationic Mn(III) N-substituted pyridylporphyrins with E1/2 > 0 mV vs NHE as efficient catalysts for ascorbate oxidation. The anticancer potential of MnPs/Asc system was subsequently tested in cellular (human MCF-7, MDA-MB-231 and mouse 4T1) and animal models of breast cancer. At the concentrations where ascorbate (1 mM) and MnPs (1 or 5 μM) alone did not trigger any alteration in cell viability, combined treatment suppressed cell viability up to 95%. No toxicity was observed with normal human breast epithelial HBL100 cells. Bell-shape relationship, essentially identical to vo(Asc)ox vs E1/2, was also demonstrated between MnP/Asc-controlled cellular cytotoxicity and E1/2-controlled vo(Asc)ox. Magnetic resonance imaging studies were conducted to explore the impact of ascorbate on T1-relaxivity. The impact of MnP/Asc on intracellular thiols and on GSH/GSSG and Cys/CySS ratios in 4T1 cells was assessed and cellular reduction potentials were calculated. The data indicate a significant increase in cellular oxidative stress induced by MnP/Asc. Based on vo(Asc)ox vs E1/2 relationships and cellular cytotoxicity, MnTE-2-PyP5+ was identified as the best catalyst among MnPs studied. Asc and MnTE-2-PyP5+ were thus tested in a 4T1 mammary mouse flank tumor model. The combination of ascorbate (4 g/kg) and MnTE-2-PyP5+ (0.2 mg/kg) showed significant suppression of tumor growth relative to either MnTE-2-PyP5+ or ascorbate alone. In addition to optimal vo(Asc)ox, the compound mu...

Antibacterial photoefficiency (throughout the text photoefficiency has been used as equivalent of photocytotoxic efficacy) can be increased by orders of magnitude by increasing the lipophilicity of cationic alkylmetalloporphyrin PSs.

Numerous reports suggest the involvement of oxidative stress in cadmium toxicity, but the nature of the reactive species and the mechanism of Cd-induced oxidative damage are not clear. In this study, E. coli mutants were used to investigate mechanisms of Cd toxicity. Effects of Cd on metabolic activity, production of superoxide radical by the respiratory chain, and induction of enzymes controlled by the soxRS regulon were investigated. In E. coli, the soxRS regulon controls defense against O·and univalent oxidants. Suppression of metabolic activity, inability of E. coli to adapt to new environment, and slow cell division were among the manifestations of Cd toxicity. Cd increased production of O· by the electron transport chain and prevented the induction of soxRS-controlled protective enzymes, even when the regulon was induced by the redox-cycling agent, paraquat. The effect was not limited to soxRS-dependent proteins and can be attributed to previously reported suppression of protein synthesis by Cd. Increased production of superoxide, combined with inability to express protective enzymes and to replace damaged proteins by de novo protein synthesis, seems to be the main reason for growth stasis and cell death in Cd poisoning.

Thirty-three healthy term infants were fed either soy formula (SF, 0.028 mumol Se/L; n = 17) or soy formula with added selenate (SF+Se, 0.17 mumol Se/L; n = 16) from birth (+4 d) to 16 wk. Selenium intakes of infants fed SF+Se were similar to the recommended dietary allowance and significantly greater than those of SF-fed infants. The SF group had significantly lower plasma, erythrocyte, and urine selenium, and lower plasma and erythrocyte glutathione peroxidase (GPx) activities at 16 wk compared to those of infants fed SF+Se. A decrease in plasma selenium was observed in SF-fed infants, whereas no differences in plasma selenium were found in infants fed SF+Se. These results indicate that selenate added to soy formula is highly available and effective at maintaining infant plasma and erythrocyte selenium concentrations and GPx activities that are greater than those of infants fed soy formula not fortified with selenium.

ZnTe -Cu thin films with Cu concentration in the range 3 -9 at% were prepared using r.f. magnetron cosputtering. XRD results showed that the films were amorphous below 250 °C, while above that temperature a polycrystalline phase with strong preferential orientation of crystallites appears. For undoped films, the XRD spectrum shows the enhancement of the 100 peak of orthorhombic ZnTe polycrystals while for the ZnTe -Cu films evidence was obtained for the presence of Cu x Zn 1-x Te phase with x near 0.20. The results of electrical measurements supports the view that the majority of Cu is in the Cu x Zn 1-x Te phase. The room temperature transmission and reflectivity were measured in the wavelength range 300 nm ≤ λ ≤ 3000 nm. The energy band gap was determined and found to vary significantly with substrate temperature. This was attributed to the appearance of band tails at the principle bands edges produced by perturbation in the local potential associated with the amorphous modification. For Cu-doped samples, further reduction in E g is brought about through merging of the Cu acceptor density-of-states with the valence band.