Combination Therapy with Sulfasalazine and Valproic Acid Promotes Human Glioblastoma Cell Death Through Imbalance of the Intracellular Oxidative Response.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes. As both drugs are widely used in clinical practice and their profile of adverse effects is well known, the aim of our study was to investigate the effects of the combined treatment with SAS and VPA in GBM cell lines. We observed that both drugs were able to reduce cell viability in a dose-dependent manner and the combined treatment potentiated these effects. Combined treatment also increased cell death and inhibited proliferation of GBM cells, while having no effect on human and rat cultured astrocytes. Also, we observed high protein expression of the catalytic subunit of xc- in all the examined GBM cell lines, and treatment with SAS blocked its activity and decreased intracellular GSH levels. Noteworthy, SAS but not VPA was also able to reduce the [14C]-ascorbate uptake. Together, these data indicate that SAS and VPA exhibit a substantial effect on GBM cell's death related to an intracellular oxidative response imbalance, making this combination of drugs a promising therapeutic strategy.

Decontamination of Mikania glomerata Leaves by Gamma Irradiation: Coumarin Determination by HPLC-DAD, Microbiological Control and Genotoxicological Studies.

Gamma irradiation as a decontaminating physical agent could be an important tool in the production chain of herbal medicines by improving the microbiological quality of raw materials and the safety of final products. This study was undertaken to investigate the genotoxic potential and eventual chemical modifications of a batch of Mikania glomerata raw material decontaminated by different doses of gamma irradiation (2.0, 3.5, and 5.0 kGy), using a cesium-137 source. DNA damage was assessed in vitro by agarose gel electrophoresis in regard to double-chain breaks of plasmid pUC 9.1 DNA and in vivo by micronucleus test in bone marrow cells of Wistar rats. Cytotoxicity in bone marrows was assessed by scoring polychromatic and normochromatic erythrocytes ratio. An HPLC-DAD method was adapted and validated for the enhancement of coumarin selectivity from the other matrix constituents. The microbial load was satisfactorily reduced, leading to sterilization at the highest dose. Genotoxic and cytotoxic effects were not increased in the in vitro and in vivo models. The concentration of coumarin and the chromatographic profiles of the hydroalcoholic plant extracts (ethanol 70% v/v) were not modified after such process. Therefore, this work suggests that gamma irradiation of M. glomerata raw material is suitable and safe for microbiological control purposes at the employed doses.

Polycyclic aromatic hydrocarbons (PAHs) in street dust of Rio de Janeiro and Niterói, Brazil: Particle size distribution, sources and cancer risk assessment.

Fifteen polycyclic aromatic hydrocarbons (PAHs) were analyzed in two fractions (<63µm and 63-850µm) of street dust samples collected in different urban areas of Rio de Janeiro and Niterói cities, Brazil. Individual PAH concentrations and total PAH concentrations (∑PAH) were evaluated considering geographic and particle size distributions, PAH source and cancer risk. In 53% of the samples, ∑PAH values were higher in the smallest particles than in the largest ones, whereas the inverse was true for 23.5% of the samples. In 23.5% of the samples, both classes of particles showed comparable ∑PAH. The highest ∑PAH concentrations were found in areas of limited air dispersion, resulting in PAH accumulation in street dust. The diagnostic ratios and principal component analysis (PCA) indicated a strong influence of pyrogenic sources on PAH concentration, mainly of vehicular emissions. The cancer risk levels for children and adults, for both particulate size fractions (<63µm and 63µm-850µm), were comparable for dermal contact and by ingestion, and ranged from 10-8 to 10-6, whereas in certain cases the cancer risk level for adults by dermal contact was 2 to 3 times larger than for children. The cancer risk levels via inhalation always ranged from 10-13 to 10-10, so this exposure pathway was almost 104 less severe than through ingestion and dermal contact, and thus negligible.

Antioxidant activity of polyphenols from green and toasted mate tea.

The production and distribution of toasted mate tea in Brazil has increased, which has resulted in its greater consumption. Mate tea is obtained by roasting non-fermented erva-mate in order to produce toasted erva-mate or toasted mate tea. However, although the product is much appreciated, studies of its chemical composition and the concentration of polyphenols, particularly flavonols present in toasted mate tea, are few and often controversial. This paper elucidates some misunderstandings involving the nomenclature of erva-mate and toasted mate, and mainly provides an overview of the composition of polyphenols and antioxidant capacity of toasted mate tea and its raw material, erva-mate, in comparison with other teas, the compositions of which were found in the literature.