Developmental toxicity, oxidative stress, and related gene expression induced by dioxin-like PCB 126 in zebrafish (Danio rerio).

Abstract

3,3',4,4',5-Pentachlorobiphenyl (PCB126) cause multiple adverse effects in organisms including animals and humans. Although PCB toxicities are linked to oxidative damage in rodents, the mechanism in early life stages of zebrafish is not clear. To explore the developmental toxicity mechanism of PCB126, three paradigms (toxicological phenotypes, biochemical changes, and molecular changes) were studied in 3-h postfertilization (hpf) zebrafish (Danio rerio) embryos exposed to different PCB126 concentrations (0, 16, 32, 64, and 128 μg/L) until 168 hpf. Developmental malformations, including pericardial and yolk sac edema, impaired lower jaw growth, spinal curvature, head edema and failure to inflate the swim bladder were observed, some as early as 72 hpf. Mortality was not apparent in early stages but significantly increased in a dose-dependent manner from 144 hpf onward. A dose-dependent significant increase in malformation rate was observed from 72 hpf onward with up to 100% at 132 hpf in embryos exposed to 128 μg/L of PCB126. Higher doses of PCB126 significantly decreased the copper-zinc superoxide dismutase (CuZn-Sod), catalase (Cat), and glutathione peroxidase (Gpx) enzyme activities at 96, 132 hpf, but markedly declined from thereafter. PCB126 at 128 μg/L significantly increased the malondialdehyde content at 72, 96, and 132 hpf. The transcriptional gene expression of antioxidant enzymes Cat and Gpx was upregulated in embryos exposed to 64 μg/L of PCB126 at 24 and 96 hpf. Sod1 messenger RNA (mRNA) was low in embryos exposed to 32 μg/L at 72 and 96 hpf but was induced in embryos exposed to 64 and 128 μg/L doses at 132 hpf. Collectively, the results suggest oxidative stress as a major factor in the induction of multiple developmental abnormalities in early life stages of zebrafish exposed to PCB126. However, the relationship between the antioxidant enzyme activity and the mRNA expression was not clear and the potential reasons for this are discussed.