Proteomic Analyses of 3-Monochloropropanediol 1-Monooleate and 1-Monostearate Induced Testicular Toxicity in a 90 Day Sprague-Dawley Rats' Study.
Proteomic Analyses of 3-Monochloropropanediol 1-Monooleate and 1-Monostearate Induced Testicular Toxicity in a 90 Day Sprague-Dawley Rats' Study.
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DOI：
10.1021/acs.jafc.0c07242
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发表时间：
2021-04
影响因子：
6.1
通讯作者：
Puyu Yang;Yaqiong Zhang;Yanfang Li;M. Granvogl;Boyan Gao;L. Yu
中科院分区：
文献类型：
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作者：
Puyu Yang;Yaqiong Zhang;Yanfang Li;M. Granvogl;Boyan Gao;L. Yu
3-1，2-二醇单氯丙烷酯（3-MCPD）是食品热加工过程中产生的有毒物质，其睾丸毒性已被广泛报道。在这项为期90天的体内研究中，Sprague-Dawley大鼠接受10和100 mg/kg体重（bw）/天的3-MCPD 1-单油酸酯或15和150 mg/kg bw/天的1-单硬脂酸酯给药。组织学检查结果显示，大鼠睾丸损伤，血清睾酮水平呈剂量依赖性下降，血清转化生长因子β和γ-干扰素水平呈剂量依赖性升高。为了解决导致3-MCPD酯睾丸毒性的分子机制，采用质谱蛋白质组学方法研究了睾丸样品。受3-MCPD酯影响的失调蛋白包括许多与炎性坏死途径相关的酶。在细胞水平验证结果的同时，3-MCPD 1-单油酸酯和3-MCPD 1-单硬脂酸酯显示出几乎相似的睾丸细胞毒性，它们可以在细胞水平激活RIPK 1和MLKL通路。这些结果揭示了3-MCPD酯类化合物对大鼠睾丸毒性的可能机制，对了解3-MCPD酯类化合物的体内外毒性作用具有重要意义。
3-Monochloropropane 1,2-diol (3-MCPD) esters are toxicants formed during food thermal processing, and their testicular toxicities were widely reported. In this 90 day in vivo study, Sprague-Dawley rats were treated with 3-MCPD 1-monooleate at 10 and 100 mg/kg body weight (bw)/day or 1-monostearate at 15 and 150 mg/kg bw/day. Histological results indicated that testicular impairment was observed, and the level of serum testosterone was decreased dose dependently, while the levels of serum transforming growth factor beta and interferon-γ in rats' serum were increased dose dependently. To address the molecular mechanisms leading to testicular toxicities of 3-MCPD esters, testes samples were investigated with a mass spectrometry proteomic approach. The deregulated proteins affected by 3-MCPD esters include many enzymes related with the inflammatory necrosis pathways. While verifying the results in cellular level, 3-MCPD 1-monooleate and 3-MCPD 1-monostearate showed almost similar testicular cytotoxicity, and they could activate RIPK1 and MLKL pathways at the cellular level. All of these results showed the possible mechanisms about the toxicity of 3-MCPD esters in rats' testes and play a vital role in understanding the toxic effects of 3-MCPD esters both in vivo and in vitro.