New Evidence on the Antiproliferative Activity of Campomanesia Adamantium (Cambess.) O. Berg Extracts in Melanoma Lung Metastasis.

Given the importance of discovering plant species from the Brazilian Cerrado biome with anticancer potential, this study evaluated the antitumor activity of two extracts of Campomanesi adamantium fruits in in vitro and in vivo models of melanoma lung metastasis. Pulp and peel extracts (DEGPU and DEGPE, respectively) were extracted from fresh fruit using dichloromethane as a solvent. As cytotoxicity parameter, concentration values that inhibited 50% cell growth (GI50), total growth inhibition (TGI), and selectivity index (SI) were established. The melanoma lung metastasis model was obtained by injecting 5 × 105/50 µL B16-F10 cells via the tail vein of mice, which received treatment on the 15th day. Metastatic lungs were collected for fluorescence analysis with the IR-780 marker and also macro- and microscopic assessment. In vitro analyses showed that DEGPU was active in K562 (GI50 32.99; TGI 47.93) and U-251 (GI50 32.10; TGI 249.92), whereas DEGPE showed better cytotoxicity results for all tumor cell lines, but was more efficient in K562 (GI50 27.42; TGI 40.20) and U-251 (GI50 4.89; TGI 12.77). Both showed a cytocidal effect on B16F10 at the highest concentration tested, with approximately 25% (DEGPU) and 88% (DEGPE) of cell death. In vivo analyzes showed that both extracts showed significant activity in metastatic lung. Fluorescence images showed differences in intensity between groups owing to greater tumor involvement. Macro- and microscopic images showed that treatments with extracts limited tumor growth and prevented proliferation. The extracts tested have promising activity, thus requiring further research on their active compounds.

Investigating Effects of IR-780 in Animal Models of B16-F10 Melanoma: New Approach in Lung Metastasis.

IR-780 is a fluorescent marker, photostable and non-toxic, and is widely used in tumor targeting; however, studies on the impact of IR-780 in animal models of B16-F10 melanoma are scarce in the literature. Therefore, this study aims to analyze behavior of this marker in melanoma cells using in vitro and in vivo analyses with fluorescence microscopy to conduct an analysis of cell culture, and an in vivo imaging system for an analysis of cell culture, tumor targeting on animals, and organ examination. In vitro analysis showed that B16-F10 cells at a concentration of 2 × 105 cells.plate-1 allowed a better visualization using 20 µM of IR-780. Furthermore, the location of IR-780 accumulation was confirmed by its fluorescence microscopy. Through in vivo studies, fluorescence was not observed in subcutaneous nodules, and it was found that animals that received intraperitoneal injection of B16-F10 cells presented ascites and did not absorb IR-780. Additionally, animals exhibiting lung metastasis showed fluorescence in ex vivo lung images. Therefore, use of the IR-780 marker for evaluating the progression of tumor growth did not demonstrate efficiency; however, it was effective in diagnosing pulmonary metastatic tumors. Although this marker presented limitations, results of evaluating pulmonary involvement through ex vivo fluorescence imaging were determined based on intensity of fluorescence.

Characterization of oxidative stress in animal model of neonatal hypoxia.

PURPOSE: To evaluate the oxidative stress in swine neonates submitted to hypoxia. METHODS: Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. RESULTS: 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets' brain tissue were analyzed. CONCLUSIONS: Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.

Characterization of oxidative stress in animal model of neonatal hypoxia

Purpose To evaluate the oxidative stress in swine neonates submitted to hypoxia. Methods Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. Results 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets’ brain tissue were analyzed. Conclusions Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.