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Abstract:The antioxidant features, polyphenolic composition and chromatographic fingerprints of the aerial parts from three Chilean endemic plants from the Paposo Valley located on the cost of the Atacama Desert were investigated for the first time using high pressure liquid chromatography coupled with photodiode array detector and electrospray ionization mass analysis (HPLC-PDA-ESI-MS) and spectroscopic methods. The phenolic fingerprints obtained for the plants were compared and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP) and quantification of the total content of phenolics and flavonoids measured by spectroscopic methods. Thirty phenolics were identified for the first time for these species, mostly phenolic acids, flavanones, flavonols and some of their glycoside derivatives, together with three saturated fatty acids (stearic, palmitic and arachidic acids). Nolana ramosissima showed the highest antioxidant activity (26.35 ± 1.02 μg/mL, 116.07 ± 3.42 μM Trolox equivalents/g dry weight and 81.23% ± 3.77% of inhibition in the DPPH, FRAP and scavenging activity (SA) assays, respectively), followed by N. aplocaryoides (85.19 ± 1.64 μg/mL, 65.87 ± 2.33 μM TE/g DW and 53.27% ± 3.07%) and N. leptophylla (124.71 ± 3.01, 44.23 ± 5.18 μM TE/g DW OPEN ACCESSMolecules 2015, 20 11491 and 38.63% ± 1.85%).

Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provoke an oxidative stress that preferentially kill cancer cells and spare healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.

Abstract. Chronic hypobaric hypoxia (CHH) induces a decrease in sperm output and spermatogenesis in male rats. The mechanisms that underlie these changes in testicular function are unknown and could involve changes in the hypophysis-gonad axis. We have tested the hypothesis that changes take place in the endocrine status (FSH, follicle stimulating hormone; LH, luteinizing hormone; testosterone) of rats subjected to CHH. Male Wistar rats were maintained under normobaric or hypobaric conditions (428 torr, 4,600 m). On days 0, 5, 15 and 30 post-exposure, 12 rats were anesthetized, their body weights were measured and blood samples were collected. The testicles were fixed in 4% formaldehyde and processed for histological analysis. In this time course, the FSH levels rose by day 5 post-exposure. On subsequent days, the FSH levels decreased in rats subjected to CHH with a tendency to remain higher than the normoxic group. The LH plasma levels decreased in rats exposed to CHH. Consistent with the decrease in LH levels, the plasma testosterone level decreased significantly after 30 days of CHH exposure. Integrated analysis of hormonal changes in rats subjected to CHH and the body dehydration that occurs in HH allows us to conclude that the effects of CHH on spermatogenesis may be partially related to changes in the hypophysis-gonad hormonal axis. Key words: Fertility, High altitude, Hypobaric hypoxia, Testicular function, Testis (J. Reprod. Dev. 54: [18][19][20][21] 2008) hronic hypobaric hypoxia (CHH) is experienced by an increasing number of sea level natives exposed to high altitude because of tourism, border patrol, mining or rural health and education activities [1]. It has been suggested that hypobaric hypoxia reduces fertility in humans. Nonetheless, epidemiological studies of high and low altitude populations have not been able to verify this proposal [2]. Based on the hormonal changes observed in men and rats at high altitude, some authors have proposed that CHH affects the hypothalamic/gonad axis (e.g. [3][4][5]). However, the results in the literature have been controversial. Nelson et al. reported that the plasma levels of GH, LH, FSH and TSH of hypoxic rats did not differ from the control values [3]. These results are in agreement with the reported absence of changes in the testosterone levels of rats exposed to hypoxia compared with sea level controls published by Gonzales et al. [5]. Instead, Sawhaney et al. [4] reported a decrease in the LH and testosterone levels in men exposed to CHH. Exposure of male rats to chronic hypobaric hypoxia and intermittent hypobaric hypoxia induced evident changes in testicular morphology [6][7][8][9], strong metabolic stress and loss of spermatogenic cells [8]. Local changes observed in testicles exposed to hypoxia include neovascularization and an increase in temperature. Thus, local changes that could lead to the observed effects on spermatogenesis do occur. However, it is highly likely that these local changes are also accompanied by changes in the hypophysis-gon...

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