Activation of aryl hydrocarbon receptor reduces carbendazim-induced cell death.

Carbendazim inhibits microtubule assembly, thus blocking mitosis and inhibiting cancer cell proliferation. Accordingly, carbendazim is being explored as an anticancer drug. Data show that carbendazim increased mRNA and protein expressions and promoter activity of CYP1A1. In addition, carbendazim activated transcriptional activity of the aryl hydrocarbon response element, and induced nuclear translocation of the aryl hydrocarbon receptor (AhR), a sign the AhR is activated. Carbendazim-induced CYP1A1 expression was blocked by AhR antagonists, and was abolished in AhR signal-deficient cells. Results demonstrated that carbendazim activated the AhR, thereby stimulating CYP1A1 expression. In order to understand whether AhR-induced metabolic enzymes turn carbendazim into less-toxic metabolites, Hoechst 33342 staining to reveal carbendazim-induced nuclear changes and flow cytometry to reveal the subG0/G1 population were applied to monitor carbendazim-induced cell apoptosis. Carbendazim induced less apoptosis in Hepa-1c1c7 cells than in AhR signal-deficient Hepa-1c1c7 mutant cells. Pretreatment with ß-NF, an AhR agonist that highly induces CYP1A1 expression, decreased carbendazim-induced cell death. In addition, the lower the level of AhR was, the lower the vitality present in carbendazim-treated cells, including hepatoma cells and their derivatives with AhR RNA interference, also embryonic kidney cells, bladder carcinoma cells, and AhR signal-deficient Hepa-1c1c7 cells. In summary, carbendazim is an AhR agonist. The toxicity of carbendazim was lower in cells with the AhR signal. This report provides clues indicating that carbendazim is more potent at inducing cell death in tissues without than in those with the AhR signal, an important reference for applying carbendazim in cancer chemotherapy.

The release and analgesic activities of morphine and its ester prodrug, morphine propionate, formulated by water-in-oil nanoemulsions.

In this study, we examined the feasibility of water-in-oil (w/o) nanoemulsions as sustained-release systems for morphine, following subcutaneous administration in rats. The ester prodrug of morphine, morphine propionate (MPR), was also utilized in this study. A variety of nanoemulsions were prepared using soybean oil or sesame oil as the external phase. Span 80, Tween 80, Plurol diisostearique and Brij 98 were used as surfactants in the w/o interface. The effects of the formulation variables on the characteristics of the nanoemulsions, such as inner droplet size, zeta potential, viscosity, drug partitioning, drug release and pharmacological effect, were evaluated. Mean sizes of nanoemulsions of 50-200 nm were obtained. The initial surface charge of the emulsions was found to be around - 3 to - 4 mV, except that the Plurol-containing vehicle showed a highly negative charge of - 23 mV. The loading of morphine and MPR into the nanoemulsions resulted in slower sustained-release behavior as compared with the drug/prodrug in aqueous solution. The rate of morphine released across the membrane was found to be highly dependent on the choice of oil and surfactant types. On the other hand, discrepancies in MPR release rates among the various formulations were minimal. The in vivo analgesic duration of morphine by targeting the drug to central nerve system could be prolonged from 1 to 3 h by incorporating the drug into nanoemulsions using Span 80 or Tween 80 as the surfactant. These results suggest that w/o nanoemulsions are well suited to provide sustained morphine delivery for therapeutic purposes.

A permeable reactive barrier for the bioremediation of BTEX-contaminated groundwater: Microbial community distribution and removal efficiencies.

This study was conducted with column experiments, batch experiments, and bench-scale permeable reactive barrier (PRB) for monitoring the PRB in the relation between BTEX (benzene, toluene, ethylbenzene, and p-xylene) decomposition efficiency and the distribution of a microbial community. To obtain the greatest amount of dissolved oxygen from oxygen-releasing compounds (ORCs), 20-d column tests were conducted, the results of which showed that the highest average amount of dissolved oxygen (DO) of 5.08 mg l(-1) (0.25 mg-O(2)d(-1)g(-1)-ORC) was achieved at a 40% level of CaO(2). In the batch experiments, the highest concentrations of benzene and toluene in which these compounds could be completely degraded were assumed to be 80 mg l(-1). Long-term monitoring for a PRB indicated that ORCs made with the oxygen-releasing rate of 0.25 mg-O(2)d(-1)g(-1)-ORC were applicable for use in the PRB because these ORCs have a long-term effect and adequately meet the oxygen demand of bacteria. The results from the DGGE of 16S rDNAs and real-time PCR of catechol 2,3-dioxygenase gene revealed the harmful effects of shock-loading on the microbial community and reduction in the removal efficiencies of BTEX. However, the efficiencies in the BTEX decomposition were improved and the microbial activities could be recovered thereafter as evidenced by the DGGE results.