日本毒性学会学術年会
The 6th International Congress of Asian Society of Toxicology
セッションID: AP-142
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Environmental chemical & Endocrine disruptor
Toxicoproteomics of the mixture of Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) in male sprague-dawley rats
*Young Woo KIMMin Young KWAKMin Ji KIMYoon A NAMBu Young CHUNGMinji KYUNGDu Yeon BANGSeong Kwang LIMMi Jung KWONMyung Chan CHOSeung Jun KWACKHyung Sik KIMByung-Mu LEE
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To investigate the effects of a mixture of DEHP and DBP on the male reproductive system, an in-vivo experiment was performed on Sprague-Dawley rats. Male rats were treated orally with DEHP (0.5, 5, 50, and 500 mg/kg), DBP (0.5, 5, 50, and 500 mg/kg), or their mixture. After one-month administration, the absolute and relative testes weights, total sperm number, sperm number per gram of testes, daily sperm production, and serum T, E2, and ASD concentrations, total glutathione, zinc and magnesium levels in the testes that had been treated with DEHP, DBP or their mixture were reduced in a dose-dependent manner. Especially, the aforementioned variables significantly decreased in the animals in the highest-mixture-dose group (500 mg/kg DEHP combined with 500 mg/kg DBP). In proteomic analysis of testis, serum, and urine, various proteins that up- and down-regulated in a dose-dependent manner were observed in the groups that were exposed to DEHP, DBP, and their mixture, respectively. Especially, heart-type fatty acid-binding protein (H-FABP), glutathione S-transferase (GST), and leukocyte elastase inhibitor A (Serpin B1a) were highly up-regulated in the highest-mixture-dose group. Moreover, the testes in rats that had been treated with the highest mixture dose were observed to manifest more severe histopathological changes than the tissues that were exposed to a single chemical. These data suggest that the mixture of DEHP and DBP could produce synergistic adverse effects on the reproductive system. Keywords: Di(2-ethylhexyl) phthalate, Dibutyl phthalate, Mixture, Reproductive toxicity, Endocrine disrupting chemicals (EDCs), Toxicoproteomics.
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