Abstract
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.
Highlights
Congenital heart defects (CHD) constitute the largest group of congenital anomalies [1]
The hallmark endpoints after dioxin-like polychlorinated biphenils (DLCs) exposure in fish consists of circulatory failure, edema, craniofacial malformation, and growth retardation leading to lethality [7,8]. 3,3’,4,4’,5-Pentachlorobiphenyl (PCB126) is the most representative coplanar congener of dioxin-like polychlorinated biphenyls (PCBs) and has similar structure and biological effects to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
PCB126 exposure leads to a cardiovascular failure manifested by the development of pericardial effusion, body shortening, altered peripheral blood flow, and cardiac performance in zebrafish larvae
Summary
Congenital heart defects (CHD) constitute the largest group of congenital anomalies [1]. The etiology of the majority of CHD remains unknown, it is likely to be multifactorial, with roles for both genetic and environmental causes. There are several epidemiological studies linking maternal exposure to environmental pollutants with occurrence of a wide range of CHD [2] and experimental studies demonstrate that the developing cardiovascular system is a sensitive target of many environmental pollutants, including dioxins, dioxin-like polychlorinated biphenils (DLCs), and some pesticides [3]. Fish are among the most sensitive vertebrates to DLC-induced teratogenicity [5]. Fish are more sensitive to these effects than mammals are, the developmental effects observed are similar to other vertebrates (mammals and birds) and phenotypically resemble some birth defects in humans [6]. While AhR activation seems to be a prerequisite for DLCs toxicity [10], the identity of the trigger gene or genes regulating teratogenesis remains unknown
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