Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 33, Issue 1, Pages 32-40Publisher
WILEY
DOI: 10.1002/jat.1708
Keywords
zebrafish; development; JNK inhibitor; AhR; sensory system; SP600125; anthrapyrazolone; toxicity; TCDD
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Funding
- Illinois Institute of Technology
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SP600125 (anthrapyrazolone) is a synthetic polyaromatic chemical that inhibits c-Jun N-terminal kinase (JNK) signaling by interfering with phosphorylation of c-Jun. To determine the pharmacological impact of SP600125 on zebrafish development, we incubated embryos in various concentrations of SP600125 from 18?h postfertilization (hpf) to 48?hpf. Embryos treated with 1.25 mu m appeared with occasional pericardium edema. Treatment with 12.5 mu m resulted in complete mortality by 120?hpf, preventing an assessment of physiological defects. Embryos treated with 5 mu m exhibited slowed overall growth, a delay in hatching and numerous morphological defects such as pericardium edema, yolk sac edema, swim bladder deflation, bent vertebrae and eye and jaw malformations. Whole-mount immunohistochemical studies using an anti-acetylated beta-tubulin antibody confirmed developmental defects in the nervous system. Within the retina, fish treated with 1.25 mu m showed a mild reduction of immunoreactivity. Immunoreactivity in the retina was further reduced in fish treated with 5 mu m of SP600125. In these fish, eyes and olfactory organs were half the size compared with other groups. Multiple lenses were observed in 67% of these fish. A second experiment with a shorter exposure period of SP600125 (6?h) presented significantly fewer morphological defects. The treatment led to a delay in hatching, and increased incidences of swim bladder deflation and pericardium edema with increasing concentrations. In summary, SP600125 caused developmental abnormalities during zebrafish organogenesis starting at 1.25 mu m and the defects were exacerbated with increasing concentrations. Our study suggests that SP600125 at 1.25 mu m and beyond has devastating consequences for zebrafish development. Copyright (C) 2011 John Wiley & Sons, Ltd.
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