1. Di-(2-ethylhexyl) phthalate (DEHP)-induced hepatotoxicity in quail (Coturnix japonica) via suppression of the heat shock response.
- Author
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Zhao, Yi, Fan, Jing-Hui, Luo, Yu, Talukder, Milton, Li, Xue-Nan, Zuo, Yu-Zhu, and Li, Jin-Long
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JAPANESE quail , *HEAT shock factors , *HEPATOTOXICOLOGY , *HEAT shock proteins , *QUAILS ,MECHANICAL shock measurement - Abstract
Di-(2-ethylhexyl) phthalate (DEHP) is a widespread environmental toxicant that severely impacts agricultural production and animal and human health. Nevertheless, DEHP-induced hepatotoxicity at the molecular level in quail remains unexplored. The heat shock response (HSR), involving heat shock proteins (HSPs) and heat shock transcription factors (HSFs), is a highly conserved molecular response that is triggered by stressors, especially exposure to toxicants. To explore the DEHP-induced hepatotoxicity that occurs via regulation of HSR in birds, female quail were dosed with DEHP by oral gavage (0, 250, 500 and 1000 mg/kg) for 45 days. Based on histopathological analysis, the livers of the DEHP-treated groups exhibited structural alterations of hepatocytes, including mitochondrial swelling, derangement of hepatic plates, inflammatory cell infiltration and adipose degeneration. Ultrastructural evaluation of the livers of DEHP-treated quail revealed swollen mitochondria, partial disappearance of mitochondrial membranes and cristae, nuclear chromatin margination and nuclear condensation. The expression of HSF1 and HSF3 significantly decreased after DEHP exposure. The levels of HSPs (HSP10, HSP25, HSP27, HSP40, HSP47, HSP60, HSP70 and HSP90) were significantly downregulated in the livers of DEHP-treated quail. In this study, we concluded that DEHP exposure resulted in liver function damage and hepatotoxicity by reducing the expression of HSFs and HSPs in quail liver, which inhibited the protective effect of the HSR signaling pathway. DEHP can be absorbed by quail via a trophic chain that eventually results in hepatotoxicity. The results of this study indicated that mitochondria are target organelles of DEHP hepatotoxicity. DEHP can activate the HSR signaling pathway and suppress HSP system homeostasis to alleviate mitochondrial dysfunction. The present study provides new insights and shows that DEHP-induced hepatotoxicity is associated with the HSR-mediated defense system. Image 1 • DEHP exposure induced hepatotoxicity. • DEHP triggered the HSR signaling pathway. • DEHP induced hepatotoxicity via suppressing of the HSR signaling pathway. • DEHP exposure resulted in hepatotoxicity via reducing HSPs and HSFs expression. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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