André L. S. Barros

Evaluation of cytotoxic and anti-inflammatory activities of extracts and lectins from Moringa oleifera seeds.

Background The extract from Moringa oleifera seeds is used worldwide, especially in rural areas of developing countries, to treat drinking water. M. oleifera seeds contain the lectins cmol and WSMoL, which are carbohydrate-binding proteins that are able to reduce water turbidity because of their coagulant activity. Studies investigating the ability of natural products to damage normal cells are essential for the safe use of these substances. This study evaluated the cytotoxic and anti-inflammatory properties of the aqueous seed extract, the extract used by population to treat water (named diluted seed extract in this work), and the isolated lectins cmol and WSMoL. Methodology/Principal Findings The data showed that the aqueous seed extract and cmol were potentially cytotoxic to human peripheral blood mononuclear cells, while WSMoL and diluted seed extract were not cytotoxic. The M. oleifera aqueous seed extract and the lectins cmol and WSMoL were weakly/moderately cytotoxic to the NCI-H292, HT-29 and HEp-2 cancer cell lines and were not hemolytic to murine erythrocytes. Evaluation of acute toxicity in mice revealed that the aqueous seed extract (2.000 mg/kg) did not cause systemic toxicity. The aqueous seed extract, cmol and WSMoL (6.25 µg/mL) and diluted seed extract at 50 µg/mL exhibited anti-inflammatory activity on lipopolyssaccharide-stimulated murine macrophages by regulating the production of nitric oxide, TNF-α and IL-1β. The aqueous seed extract reduced leukocyte migration in a mouse model of carrageenan-induced pleurisy; the myeloperoxidase activity and nitric oxide, TNF-α and IL-1β levels were similarly reduced. Histological analysis of the lungs showed that the extract reduced the number of leukocytes. Conclusion/Significance This study shows that the extract prepared according to folk use and WSMoL may be non-toxic to mammalian cells; however, the aqueous seed extract and cmol may be cytotoxic to immune cells which may explain the immunosuppressive potential of the extract.

Avaliação do controle radioquímico do Ricinus communis L. e Tc-99m na marcação de hemácias

Ricinus communis L. belongs to the Euphorbiaceae family, from whose fruits the ricin oil is extracted, highly toxic. In this study it was analyzed the effect of the extract of Ricinus communis L. in the labeling of red blood cells with Tc-99m through the radiochemical control. The results showed that in the radiochemical control through chromatography, it was observed that the extract labeled with Tc-99m showed two fractions with 130.007 and 494.592 cpm, and in the labeling of red blood cells, with %ATI of 61.88 and 41.32% in the fractions 1 and 2. It has been concluded that the extract of Ricinus communis alters the captivating of Tc-99m in vitro, competing with the radioactive material in the possible binding sites of the red blood cells, as well in the capacity of oxidation of the stannous ion or by competition with the pertechnetate ion.

Preclinical Validation of the Located Hyperthermia Using Gold Macro-Rods and Ultrasound as an Effective Treatment for Solid Tumors

Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. In this study used a method for inducing hyperthermia in solid tumors with a combination of gold macro rod (GR) and ultrasound, the feasibility of this technique was described only with computational models and in vitro. The Ehrlich tumor, derived from a mouse adenocarcinoma, has been used to investigate the bio-heat transfer and the effect of gold rods irradiated with ultrasound. The in vivo measurements demonstrated that the technique inhibited more 80% of the tumor growth in both experimental models tested. These results not only confirm the bio heat transfer to tissue as predicted by analytical calculation and in vitro measurements, but are also proved to be a potential alternative to kill cancer cells.

N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression

BACKGROUND Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells. METHODS Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR. RESULTS NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased. CONCLUSION The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.

SU-F-E-05: Determination of Breakeven Points of in Vitro Meats and in Vivo Mice Based On Tissue Temperature Enhancement Pattern

PURPOSE To determine the breakeven points in fresh commercial meat and in vivo mice using the tissue temperature enhancement pattern. METHODS A 1 cm length and 0.1 cm diameter gold rod were implanted in fresh chicken breast, beef, fish, in vivo Mus Musculus white mice (medial dorsal region) and insonated with ultrasound. The temperature enhancement of gold rods was measured with a needle type thermistor over a temperature range from 35-50 oC. From these results the breakeven points were determined by plotting the gold rod temperature versus ultrasound exposure time and determining the interception point of two curves fitted by a linear regression of thermal response above and below 43 °C. RESULTS The linear correlation coefficients for all fitted curves lie within 0.97 and 0.99. The breakeven points were found to be the same for all kinds of fresh meat (fish = 42.1 ±1.1, chicken breast = 42.3 ±0.9, beef = 42.6 ±0.8) and in vivo Mus Musculus white mice (43.3 ±0.6). These temperatures agree with the standardized value (e.g. equivalent minutes at 43 °C) for comparison of thermal treatments (Proc. SPIE Int. Soc. Opt. Eng. 2003 June 2; 4954: 37). CONCLUSION The interception of the thermal response curves above and below 43 °C may be used as a fast method and useful dosimetric tool in clinical research.

SU‐F‐E‐04: A Paris System‐Based Implant Approach to Hyperthermia Cancer Tumor with Gold Seeds and Ultrasound

PURPOSE To apply the Paris system-based implant for an uniform bio-heat distribution from implanted gold rods in tissue insonated with ultrasound. METHODS Experiments with single-plane implants using parallel equidistant 1.018 ± 0.015 cm height and 0.136 ± 0.001 cm diameter 24-K gold rods) arranged in triangular and square shapes were performed in Mus Musculus white mice (medial dorsal region). The mice were anesthetized and gold rods were implanted by means of a trocar needle and the implanted region was insonated with a 4-cm diameter transducer oscillating with a nominal frequency of 1 MHz and power of about 75 W. Intramuscular tissue temperature measurements were taken using implantable needle type thermocouples affixed to a portable Fluke thermometer. Superficial tissue temperature profile was also measured with a FLIR infrared camera and thermographic analysis were performed using the ImageJ computer software. In both cases, the central implant planes have been assigned to that approximately bisects all the implanted rods. RESULTS Measured with the needle type thermistor, for the triangular implant, the percentage deviation between the maximum and minimum temperature within the triangular plane was 5%. For a square shape, this percentage deviation was 6%. The thermographic analysis have shown a deviation of 3% and 5% for the triangular and square shapes, respectively. CONCLUSION Based on the temperature measurements with needle type thermistor and thermographic analysis, the Paris system-based implant approach for gold rods implanted in tissue and exposed to ultrasound may greatly improve the bio-heat propagation and sustain a constant temperature profile inside triangular and square patterns formed by gold rods implants. Additionally, the Paris system may minimize ablations areas and treatment length in hyperthermia if used in cancer tumor treatment.