Studies On Developmental Toxicology Of Dioxin-like PCB126in Zebrafish Embryos

Dioxin-like polychlorinated biphenyls (DlPCBs), with the toxicology of being similarto dioxins, are sorts of the most toxic polychlorinated biphenyls (PCBs). Because of theirhigh lipophilicity and biomagnification, DlPCBs can bioaccumulate and biomagnifythrough ecological food chains and concentrate in both animals and human beings.Previous studies have demonstrated that some DIPCBs have been found in a variety offoodstuffs, including seafood, meat products, and also in human breast milk. DlPCBs, asenvironmental endocrine disruptors, have many adverse effects, such as immunotoxicity,reproductive toxicity, developmental toxicity, dermal toxicity, and neurotoxicity and so on.Recently, there were some reports about developmental toxicity in children, which havearoused great concern by some researchers. Some studies have demonstrated that DIPCBscould cause some developmental toxicity in early life-stages of fish, includingcardiovascular circulation barrier, hypoevolutismus and so on. However, developmentaltoxicity in zebrafish embryos exposure to DlPCBs is little known, and the potentialtoxicological mechanism is not clear. Thus, the present study employed zebrafish embryosto explore the mechanism of developmental toxicity of dioxin-like PCB126. It was aimedto comprehensively study the developmental toxicological mechanisms of PCB126by:(1)Identifying the developmental malformations, survival rate, pericardial and yolk sac edemarate, heart rate and hatching rate in different exposure times.(2) Evaluating the in vivo7-ethoxyresorufin-O-deethylase (EROD) activity and cytochrome4501A (cyp1a) genemRNA expression at24,72,96and132hours post fertilization (hpf) exposure to explorewhether the toxicity of PCB126was associated with aryl hydrocarbon recepter (AhR)pathway.(3) To understand the mechanism of developmental toxicity induced by PCB126focusing on oxidative stress in zebrafish embryos better, malondialdehyde (MDA), aproduct of lipid peroxidation was measured, and the activities of antioxidant enzymes,copper zinc superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathioneperoxidase (GPX), as well as the mRNA expressions of those3enzymes, sod1, cat and gpx,were studied at24,72,96, and132hpf exposure to different concentrations of PCB126,respectively. The results were as follows:1. PCB126aroused developmental toxicity in zebrafish embryos. Certain doses ofPCB126exposure to zebrafish embryos caused a range of developmental malformations, including pericardial and yolk sac edema, lower jaw growth, spinal curvature, non-inflatedswim bladders, and cephalledema. The embryonic survival rate decreased since132hpf andall individuals dead after168hpf exposure to128μg/L of PCB126. The pericardial and yolksac edema rate significantly increased but the heart rate declined since96hpf comparedwith the control group, and the pericardial and yolk sac edema rate increased in a time-anddose-dependent manner. PCB126did not alter the hatching rate.2. PCB126induced the EROD activity and cyp1a mRNA expression of zebafishembryos, which also appeared in a dose-dependent manner. Different concentrations ofPCB126increased EROD activity after72hpf exposure, and the EROD activity in embryosexposure to64and128μg/L of PCB126increased significantly (P<0.01); All PCB126exposure groups induced EROD activity except16μg/L of PCB126at96and132hpf.Induction of cyp1a mRNA expression was significantly up-regulated in zebrafish exposedto32μg/L,64μg/L at24and72hpf (P<0.01). Since96hpf, cyp1a mRNA expression ofembryos exposure to64μg/L,128μg/L of PCB126dramatically increased (P<0.01); At132hpf, the up-regulation was the greatest, with values of23.56-,89.56-and35.36-fold in16μg/L,64μg/L,128μg/L PCB126-treated groups, respectively (P<0.01).3. PCB126decreased the activities of CuZn-SOD, CAT and GPX but increased MDAcontent, while no obvious change in sod1, cat and gpx mRNA expression except for theembryos exposure to64μg/L of PCB126. PCB126significantly decreased the activities ofCuZn-SOD, CAT and GPX at96and132hpf (P<0.01) but from132hpf onwards declinedmarkedly in a dose-dependent manner; The128μg/L of PCB126significantly increasedMDA content at72,96and132hpf (P<0.01). It did not exhibit any significant difference insod1, cat and gpx mRNA expressions except64μg/L of PCB126exposure at24,72,96,and132hpf.