Cu(Nor)2·5H2O, a complex of Cu(II) with Norfloxacin: theoretic approach and biological studies. Cytotoxicity and genotoxicity in cell cultures.

Norfloxacin is a fluoroquinolone antibiotic used in the treatment of bacterial infections. In this article, we studied the potential antitumoral action of a complex of Norfloxacin with Cu(II), Cu(Nor)(2)·5H(2)O on osteosarcoma cells (UMR106) and calvaria-derived cells (MC3T3-E1), evaluating its cytotoxicity and genitoxicity. We have also elucidated the more stable conformation of this complex under physiologic conditions by Molecular Dynamic simulations based on the model of the canonical ensemble and PM6 force field. When solvent effect was taken into account, the complex conformation with both carbonyl groups in opposite sides displayed lower energy. Cu(Nor)(2)·5H(2)O caused an inhibitory effect on the proliferation on both cell lines from 300 µM (P < 0.01). Nevertheless, the decline on cell proliferation of UMR106 cells was more pronounced (45 % vs basal) than in MC3T3-E1 cells (20 % vs basal) at 300 µM (P < 0.01). Cu(Nor)(2)·5H(2)O altered lysosomal metabolism (Neutral Red assay) in a dose-dependent manner from 300 µM (P < 0.001). Morphological studies showed important transformations that correlated with a decrease in the number of cells in a dose-dependent manner. Moreover, Cu(Nor)(2)·5H(2)O caused statistically significant genotoxic effects on both osteoblast cell lines in a lower range of concentrations (Micronucleus assay) (P < 0.05 at 10 µM, P < 0.001 from 25 to 50 µM). UMR106 cells displayed a dose-related genotoxic effect between 5 and 25 µM while the MC3T3-E1 cells showed a narrower concentration dependent range. Altogether, these results suggest that Cu(Nor)(2)·5H(2)O is a good candidate to be further evaluated for alternative therapeutics in cancer treatment.

Serum levels of selenium in patients with breast cancer before and after treatment of external beam radiotherapy.

BACKGROUND: To evaluate the influence of radiotherapy on the selenium serum levels of breast cancer patients. PATIENTS AND METHODS: This prospective study includes 209 breast cancer patients treated by external beam radiotherapy from December 2007 until August 2008. Plasma selenium concentrations were determined before and at the end of the radiotherapeutic treatment. Age, clinical stage, prior chemotherapy, body mass index (BMI) and personal habits (smoking and alcoholism) were recorded for each patient. RESULTS: The mean age was 61 years; the mean BMI was 28.7. One hundred and seventy-four patients (83.3%) were nonsmokers. One hundred and eighty-nine patients (90.4%) showed no drinking habits and 110 (52.6%) have no prior chemotherapy. Sixty patients (28.7%) were in clinical stage I, 141 (67.5%) in clinical stage II and 8 (3.8%) in clinical stage III. At the beginning of radiotherapy, the mean selenium value for all patients was 86.4 µg/l and after radiation this value dropped to 47.8 µg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P > 0.001), BMI (P > 0.001), smoking (P > 0.001), alcoholism (P > 0.001), chemotherapy (P > 0.001) and clinical stage (P > 0.001). CONCLUSIONS: Significant reduction in plasma levels of selenium is recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.

Serum concentrations of vitamin A and oxidative stress in critically ill patients with sepsis.

INTRODUCTION: Sepsis is one of the main causes of mortality in patients in Intensive Care Units. As a result of the systemic inflammatory response and of the decrease of the aerobic metabolism in sepsis, the oxidative stress occurs. Vitamin A is recognized by the favorable effect that it exerts on the immune response to infections and antioxidant action. OBJECTIVE: To bring new elements for reviewing of the nutritional support addressed to critically ill patients with sepsis, with emphasis to vitamin A. METHODS: Critically ill patients with sepsis had circulating concentrations of retinol, beta-carotene, thiobarbituric acid-reactive substances (TBARS) and C-reactive protein (CRP) measured in Medicosurgical Intensive Care Unit in the city of Rio de Janeiro, Brazil. The patients were divided into two groups: patients who were receiving nutritional support and those without support. At the act of the patient's admission, APACHE II score was calculated. RESULTS: 46 patients were studied (with diet n = 24 and without diet n = 22). Reduced levels of retinol and beta-carotene were found in 65.2% and 73.9% of the patients, respectively. Among the patients who presented lower concentrations of CRP it was found higher beta-carotene inadequacy (64.8%) and 50% of retinol inadequacy. There was no significant difference as regards retinol, TBARS and APACHE II levels among the patients with and without nutritional support. However, higher levels of CRP (p = 0.001) and lower levels of serum beta-carotene (p = 0.047) were found in patients without nutritional support. CONCLUSIONS: Septic patients presented an important inadequacy of retinol and beta-carotene. The present study bring elements to the elaboration/review of the nutritional protocol directed to the group studied, especially as regards vitamin A intake.