Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma

Concentrações de retinol e de beta-caroteno séricos e perfil nutricional de crianças em Teresina, Piauí, Brasil Serum concentrations of retinol and beta-carotene, and nutritional status of children in Teresina, Piauí, Brazil

OBJETIVO: Avaliar as concentrações séricas de retinol e beta-caroteno de pré-escolares em Teresina, Piauí, com caracterização do perfil antropométrico e do consumo alimentar. MATERIAL E MÉTODOS: Estudo transversal envolvendo 135 crianças em creche municipal, com avaliação do estado nutricional pelos métodos: bioquímico (concentração sérica de retinol e beta-caroteno), antropométrico (índices de peso para estatura - P/E e estatura para idade - E/I) e dietético (freqüência de consumo alimentar). RESULTADOS: Observou-se prevalência de deficiência de vitamina A (DVA) de 8,9% (IC95%: 4,7 - 15,0%) e existência de associação entre suplementação anterior e concentrações de retinol, com maior proporção de crianças com níveis normais de retinol entre as suplementadas (p = 0,025). As concentrações de retinol e de beta-caroteno mostraram-se correlacionadas, porém com força leve a moderada (p < 0,021). Os percentuais de crianças com baixo P/E e de baixa E/I foram de 1,9% (IC95%: 0,2 - 6,8%) e 9,7% (IC95%: 4,8 - 17,1%), respectivamente. Na avaliação dietética verificou-se baixo consumo de alimentos ricos em vitamina A. CONCLUSÕES: A elevada prevalência de DVA nas crianças, combinada com a alta percentagem de crianças com valores aceitáveis de retinol, os baixos valores medianos de beta-caroteno, a alta percentagem de déficit estatural e a inadequação do consumo de alimentos ricos em vitamina A, indicam a necessidade de se aprimorar as estratégias de educação em saúde e nutrição da população, incentivando o consumo de alimentos fontes de vitamina A, como medidas auto-sustentáveis importantes no combate ao problema. Além disso, deve ser considerado o incentivo à fortificação dos alimentos e ao fortalecimento de Programas de suplementação.<br>OBJECTIVE: To evaluate serum concentrations of retinol and beta-carotene of children in Teresina, Piauí, Brazil, and to evaluate their anthropometric profile and consumption of food sources of vitamin A. METHODS: Cross-sectional study of 135 children from 36 to 83 months of age who attended a public child day care center. Nutritional status was evaluated by: biochemical (serum concentrations of retinol and beta-carotene), anthropometric (weight for height - W/H and height for age - H/A indexes), and dietary (frequency of consumption of food sources of vitamin A) methods. RESULTS: The prevalence of vitamin A deficiency (VAD) was 8.9% (95%CI: 4.7-15.0%). An association between previous supplementation with vitamin A and serum concentrations of retinol was observed, with a higher proportion of children with normal concentrations of retinol among those supplemented (p=0.025). There was a weak to moderate statistically significant correlation between the concentrations of retinol and beta-carotene, (p<0.021). The prevalence of low W/H and low H/A was respectively 1.9% (95%CI: 0.2-6.8%) and 9.7% (95%CI: 4.8-17.1%). The dietary evaluation showed low consumption of foods rich in vitamin A. CONCLUSIONS: The high prevalence of VAD combined to the prevalence of children with acceptable concentrations of retinol, low median concentrations of beta-carotene, low H/A, and inadequate ingestion of foods rich in vitamin A, reinforce the need to improve health and nutrition education in this population. Based on these results, we recommend the ingestion of foods rich in vitamin A, as an important policy to deal with this nutritional problem. Efforts are also necessary to maintain food fortification and supplementation Programs