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Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos.

Antioxidants (Basel, Switzerland) (2020-08-17)
Yi-Chen Lin, Chang-Yi Wu, Chin-Hwa Hu, Tun-Wen Pai, Yet-Ran Chen, Wen-Der Wang
ABSTRACT

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon formed by the incomplete combustion of organic matter. Environmental B[a]P contamination poses a serious health risk to many organisms because the pollutant may negatively affect many physiological systems. As such, chronic exposure to B[a]P is known to lead to locomotor dysfunction and neurodegeneration in several organisms. In this study, we used the zebrafish model to delineate the acute toxic effects of B[a]P on the developing nervous system. We found that embryonic exposure of B[a]P downregulates shh and isl1, causing morphological hypoplasia in the telencephalon, ventral thalamus, hypothalamus, epiphysis and posterior commissure. Moreover, hypoxia-inducible factors (hif1a and hif2a) are repressed upon embryonic exposure of B[a]P, leading to reduced expression of the Hif-target genes, epo and survivin, which are associated with neural differentiation and maintenance. During normal embryogenesis, low-level oxidative stress regulates neuronal development and function. However, our experiments revealed that embryonic oxidative stress is greatly increased in B[a]P-treated embryos. The expression of catalase was decreased and sod1 expression increased in B[a]P-treated embryos. These transcriptional changes were coincident with increased embryonic levels of H2O2 and malondialdehyde, with the levels in B[a]P-treated fish similar to those in embryos treated with 120-μM H2O2. Together, our data suggest that reduced Hif signaling and increased oxidative stress are involved in B[a]P-induced acute neurotoxicity during embryogenesis.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Benzo[a]pyrene, ≥96% (HPLC)