Antioxidant potential of nanomaterials.

Background/aim: The novel field of nanomaterials allows infinite possibilities in order to create antioxidant therapies. The present review is aimed to describe the state of art concerning on nanomaterials and their effects on reactive oxygen species (ROS) production. A wide range of nanoparticles has been designed for this purpose, and each one possesses some particular characteristics which allow these significant antioxidant results. Several in vivo and in vitro works state the ability of these nanoparticles to mimic the redox systems of the cells, and thus, the potential role of nanoparticles as antioxidant treatment for several diseases. Materials and methods: This paper was written after a review of the articles published on the field, using the "PubMed" and "Research Gate" databases. Results: The main types of nanoparticles are listed and explained below, offering a global vision of the field with great interest for research. Antitumor chemo- and radiotherapies have been found to improve efficacy by enhancing the selectivity of cytocidal effects and minimizing systemic adverse effects when such materials are used. Furthermore, catalytic nanomaterials can execute energy-free antioxidant cycles that scavenge the most harmful reactive oxygen species via SOD- and catalase-like activities. Conclusion: This unique method is projected to result in significant gains in the long run. However, due to a lack of understanding of potential adverse body reactions to these novel strategies, caution must be exercised. Analyzing the biocompatibility of these nanomaterials carefully, particularly in terms of biokinetics and the problems that could arise from long-term retention of nonbiodegradable inorganic nanomaterials, is required.

Cytotoxic Effects of New Palladium(II) Complexes with Thiazine or Thiazoline Derivative Ligands in Tumor Cell Lines.

The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl2(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC50 values, which ranged between 46.39 ± 3.99 µM and 62.74 ± 6.45 µM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.

Melatonin increases the effect of 5-fluorouracil-based chemotherapy in human colorectal adenocarcinoma cells in vitro.

Melatonin has antitumor activity via several mechanisms including its anti-proliferative and pro-apoptotic effects. Moreover, it has been proven that melatonin in combination with chemotherapeutic agents enhances chemotherapy-triggered apoptosis in several types of cancer. Therefore, this study was intended to evaluate whether melatonin is able to strengthen the anti-cancer potential of different chemotherapeutic drugs in human colorectal adenocarcinoma HT-29 cells. We found that treatment with 20 µM cisplatin (CIS) or 1 mM 5-fluorouracil (5-FU) for 72 h induced a decrease in HT-29 cell viability. Furthermore, 1 mM melatonin significantly (P < 0.05) increased the cytotoxic effects of 5-FU. Likewise, simultaneous stimulation with 1 mM melatonin and 1 mM 5-FU significantly (P < 0.05) enhanced the ratio of cells with an overproduction of intracellular reactive oxygen species and substantially augmented the population of apoptotic cells compared to the treatment with 5-FU alone. Nonetheless, melatonin only displayed moderate chemosensitizing effects in CIS-treated HT-29 cells, as suggested by a slight increment in the fraction of early apoptotic cells that was observed only after 48 h. Consistently, co-stimulation of HT-29 cells with 20 µM CIS or 1 mM 5-FU in the presence of 1 mM melatonin further increased caspase-3 activation. Apart from this, the cytostatic activity displayed by CIS due to S phase arrest was not affected by concomitant stimulation with melatonin. Overall, our results indicate that melatonin increases the sensitivity of HT-29 cells to 5-FU treatment and, consequently, the indolamine could be potentially applied to colorectal adenocarcinoma treatment as a potent chemosensitizing agent.

Melatonin diminishes oxidative damage in sperm cells, improving assisted reproductive techniques.

Sperm preparation procedures are a potential generator of oxidative stress-induced DNA damage, which leads to a dramatic drop in fertility. An increasing number of studies suggest that melatonin reduces the oxidative stress induced by manipulation. However, very little is known about the preservative role of melatonin in sperm preparation medium during assisted reproduction procedures. For this aim to be achieved, semen was divided into two fractions and preincubated with and without 1 mM melatonin. Afterwards, both fractions were divided into two subfractions to perform swim-up in the presence and absence of 1 mM melatonin. Labeling with anti-CD46 and antiactive caspase-3 allowed the monitoring of acrosome reaction and apoptosis by flow cytometry. Sperm DNA fragmentation and compaction were analyzed through propidium iodide staining. The normozoospermic and oligozoospermic samples that were preincubated with melatonin underwent a significant increase in the ratio of adequate spermatozoa and a reduction of caspase-3 activation. Additionally, preincubation with melatonin enhanced the migration of sperm cells with compacted DNA in oligozoospermic samples (P < 0.05) and prevented DNA fragmentation in normozoospermic samples (P < 0.05). In light of the current results, the cytoprotective capacity and innocuousness of melatonin make it a great candidate to be applied in assisted reproduction techniques in order to prevent triaogenic oxidative damage.

Bioavailability of Bioactive Molecules from Olive Leaf Extracts and its Functional Value.

Olive leaves are an important low-cost source of bioactive compounds. The present study aimed to examine the effect of in vitro digestibility of an olive leaf aqueous extract so as to prove the availability of its phenolic compounds as well as its antioxidant, antimicrobial, and anticancer activity after a simulated digestion process. The total phenolic content was significantly higher in the pure lyophilized extract. Phenolic compounds, however, decreased by 60% and 90% in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), respectively. Regarding antioxidant activity, it was reduced by 10% and 50% after gastric and intestinal digestion, respectively; despite this fact, high antioxidant capacity was found in both SGF and SIF. Moreover, the olive leaf extract showed an unusual combined antimicrobial action at low concentration, which suggested their great potential as nutraceuticals, particularly as a source of phenolic compounds. Finally, olive leaf extracts produced a general dose-dependent cytotoxic effect against U937 cells. To sum up, these findings suggest that the olive leaf aqueous extract maintains its beneficial properties after a simulated digestion process, and therefore its regular consumption could be helpful in the management and the prevention of oxidative stress-related chronic disease, bacterial infection, or even cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells through regulation of calcium release and caspase-3 and -9 activities.

Selenium is an essential chemopreventive antioxidant element to oxidative stress, although high concentrations of selenium induce toxic and oxidative effects on the human body. However, the mechanisms behind these effects remain elusive. We investigated toxic effects of different selenium concentrations in human promyelocytic leukemia HL-60 cells by evaluating Ca(2+) mobilization, cell viability and caspase-3 and -9 activities at different sample times. We found the toxic concentration and toxic time of H(2)O(2) as 100 microM: and 10 h on cell viability in the cells using four different concentrations of H(2)O(2) (1 microM: -1 mM: ) and six different incubation times (30 min, 1, 2, 5, 10, 24 h). Then, we found the therapeutic concentration of selenium to be 200 nM: by cells incubated in eight different concentrations of selenium (10 nM: -1 mM: ) for 1 h. We measured Ca(2+) release, cell viability and caspase-3 and -9 activities in cells incubated with high and low selenium concentrations at 30 min and 1, 2, 5, 10 and 24 h. Selenium (200 nM: ) elicited mild endoplasmic reticulum stress and mediated cell survival by modulating Ca(2+) release, the caspases and cell apoptosis, whereas selenium concentrations as high as 1 mM: induced severe endoplasmic reticulum stress and caused cell death by activating modulating Ca(2+) release, the caspases and cell apoptosis. In conclusion, these results explained the molecular mechanisms of the chemoprotective effect of different concentrations of selenium on oxidative stress-induced apoptosis.

Ebselen increases cytosolic free Ca2+ concentration, stimulates glutamate release and increases GFAP content in rat hippocampal astrocytes.

We have investigated the effect of the seleno-organic compound and radical scavenger ebselen on rat hippocampal astrocytes in culture. Throughout our study we carried out determinations of [Ca2+](c) in fura-2-loaded cells by single cell imaging, glutamate secretion employing an enzymatic-based assay and GFAP expression, which was monitorized by immunocytochemistry and confocal microscopy. Our results show that ebselen (1-20microM) dose dependently increases [Ca2+](c), stimulates glutamate release and increases GFAP content, a hallmark of astrocyte reactivity. Ebselen did not alter significantly cell viability as assayed by determination of LDH release into the extracellular medium. Ebselen-evoked glutamate release and increase in GFAP content were Ca2+-dependent, because incubation of astrocytes in the absence of extracellular Ca2+ (medium containing 0.5mM EGTA) and in the presence of the intracellular Ca2+ chelator BAPTA (10microM) significantly reduced ebselen-evoked changes in these parameters. The effects of ebselen we have observed may underline various signalling pathways which are important for cell proliferation, differentiation and function. However, aberrations in astroglial physiology could significantly compromise brain function, due to their role as modulators of neuron activity. Therefore, we consider that careful attention should be paid when employing ebselen as a prophylactic agent against brain damage.

Reduced plasma membrane Ca2+-ATPase function in platelets from patients with non-insulin-dependent diabetes mellitus.

We clearly show that plasma membrane Ca2+ ATPase (PMCA) activity is lower in platelets from patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those from healthy controls. The lower activity is likely due to reduced PMCA expression and increased tyrosine phosphorylation. These findings provide an explanation for the cellular ionic defects occurring in insulin resistant conditions.