Cardiovascular Effects of PCB 126 (3,3',4,4',5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals.

The developing cardiovascular system of zebrafish is a sensitive target for many environmental pollutants, including dioxin-like compounds and pesticides. Some polychlorinated biphenyls (PCBs) can compromise the cardiovascular endothelial function by activating oxidative stress-sensitive signaling pathways. Therefore, we exposed zebrafish embryos to PCB126 or to several redox-modulating chemicals to study their ability to modulate the dysmorphogenesis produced by PCB126. PCB126 produced a concentration-dependent induction of pericardial edema and circulatory failure, and a concentration-dependent reduction of cardiac output and body length at 80 hours post fertilization (hpf). Among several modulators tested, the effects of PCB126 could be both positively and negatively modulated by different compounds; co-treatment with α-tocopherol (vitamin E liposoluble) prevented the adverse effects of PCB126 in pericardial edema, whereas co-treatment with sodium nitroprusside (a vasodilator compound) significantly worsened PCB126 effects. Gene expression analysis showed an up-regulation of cyp1a, hsp70, and gstp1, indicative of PCB126 interaction with the aryl hydrocarbon receptor (AhR), while the transcription of antioxidant genes (sod1, sod2; cat and gpx1a) was not affected. Further studies are necessary to understand the role of oxidative stress in the developmental toxicity of low concentrations of PCB126 (25 nM). Our results give insights into the use of zebrafish embryos for exploring mechanisms underlying the oxidative potential of environmental pollutants.

Comparison of migration disturbance potency of epigallocatechin gallate (EGCG) synthetic analogs and EGCG PEGylated PLGA nanoparticles in rat neurospheres.

Epigallocatechin gallate (EGCG), the main catechin of green tea, is described to have potential health benefits in several fields like oncology, neurology or cardiology. Currently, it is also under pre-clinical investigation as a potential therapeutic or preventive treatment during pregnancy against developmental adverse effects induced by toxic substances. However, the safety of EGCG during pregnancy is unclear due to its proven adverse effects on neural progenitor cells' (NPCs) migration. As lately several strategies have arisen to generate new therapeutic agents derived from EGCG, we have used the rat 'Neurosphere Assay' to characterize and compare the effects of EGCG structurally related compounds and EGCG PEGylated PLGA nanoparticles on a neurodevelopmental key event: NPCs migration. Compounds structurally-related to EGCG induce the same pattern of NPCs migration alterations (decreased migration distance, decreased formation of migration corona, chaotic orientation of cellular processes and decreased migration of neurons at higher concentrations). The potency of the compounds does not depend on the number of galloyl groups, and small structure variations can imply large potency differences. Due to their lower toxicity observed in vitro in NPCs, 4,4'-bis[(3,4,5-trihydroxybenzoyl)oxy]-1,1'-biphenyl and EGCG PEGylated PLGA nanoparticles are suggested as potential future therapeutic or preventive alternatives to EGCG during prenatal period.

Developmental effects and genotoxicity of 10 water disinfection by-products in zebrafish.

Disinfection by-products are contaminants produced during drinking water disinfection. Several DBPs have been implicated in a variety of toxic effects, mainly carcinogenic and genotoxic effects. Moreover, DBPs exposure has also been associated with an increased risk of developmental effects. In this study, the developmental toxicity and genotoxicity of 10 DBPs (four trihalomethanes [THMs], five haloacetic acids [HAAs] and sodium bromate) in the zebrafish embryo model were evaluated. Embryos exposed for 72 hours were observed for different endpoints such as growth, hatching success, malformations and lethality. THMs exposure resulted in adverse developmental effects and a significant reduced tail length. Two HAAs, tribromoacetic acid and dichloroacetic acid, along with sodium bromate were found to cause a significant increase in malformation rate. Chloroform, chlorodibromomethane and sodium bromate produced a weak induction of DNA damage to whole embryos. However, developmental effects occurred at a range of concentrations (20-100 µg/mL) several orders of magnitude above the levels that can be attained in fetal blood in humans exposed to chlorinated water. In conclusion, the teratogenic and genotoxic activity observed by some DBPs in zebrafish reinforce the view that there is a weak capacity of disinfection products to cause developmental effects at environmentally relevant concentrations.

Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in Catalonia, Spain.

Monofunctional inducers (MIs) enhance phase 2 enzymes such as nicotinamide-adenine-dinucleotide-phosphate [NAD(P)H] quinone oxidoreductase (NQO1) without modifying oxidation enzymes. The induction of these protective enzymes appears to be mediated by genetic regulatory elements in their promoter regions known as the antioxidant response element (ARE). The aim of this study was to identify, through an in vitro study, which of the 30 fruits and vegetables commonly consumed in Catalonia, Spain, contain MIs of NQO1. We assayed the capacity of extracts of these fruits and vegetables to induce NQO1 [by more than 1.5-fold: ratio of induction (cells treated/control) >1.5, 8-mg/ml dose] in two murine hepatoma cell lines: Hepa 1c1c7 and BPrC1, a modified cell line that possesses a nonfunctional aryl hydrocarbon receptor nuclear translocator system and is thus nonresponsive to bifunctional inducers. We also used a third cell line, papiloma (PE) murine keratinocytes, a stably transfected cell line with an ARE-luc+ plasmid (AREPE cell line) for verifying induction through the ARE with a simple luminescence screening assay. Broccoli (Hepa 1c1c7, ratio=5.5; BPrC1, ratio=2.3), calcot (Allium cepa L.) (Hepa 1c1c7, ratio=4.7; BPrC1, ratio=.5), green onion (Hepa 1c1c7, ratio=4.6; BPrC1, ratio=2), green cabbage (Hepa 1c1c7, ratio=3.6; BPrC1, ratio=2.7), purple cabbage (Hepa 1c1c7, ratio=3.4; BPrC1, ratio=2), and black cabbage (Hepa 1c1c7, ratio=3; BPrC1, ratio=3) were active NQO1 inducers in both murine hepatoma cell lines. Extracts from broccoli (ratio=3.5), calcot (ratio=4.8), cauliflower (ratio=4.2), cabbage (ratio=2.2), green onion (ratio=3.2), green cabbage (ratio=3.6), black cabbage (ratio=4.5), and purple cabbage (ratio=3.7) were confirmed to contain MIs in the AREPE cell line. These results are very similar to those described for vegetables consumed in the United States, with the exception of calcot, which is common in Catalonia but is not grown or consumed widely in the United States.