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Evaluation of hypopigmentation in embryonic zebrafish induced by emerging disinfection byproduct, 3, 5-di-I-tyrosylalanine.
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2020-06-23 , DOI: 10.1016/j.aquatox.2020.105525
Lei Peng 1 , Chang Wang 2 , Pingdeng Li 1 , Bo Cheng 3 , Yeli Hu 3 , Yang Cheng 4 , Qi Zheng 5
Affiliation  

Halogenated dipeptides, 3, 5-di-I-tyrosylalanine (DIYA), have been identified as novel disinfection byproducts (DBPs), following chloramination of authentic water. However, little is known about their toxicity. Zebrafish embryos were used to assess the toxicity of novel iodinated DBPs (I-DBPs). Although DIYA did not exhibit high acute toxicity to embryonic zebrafish (LC50 > 2 mM), it significantly inhibited pigmentation of melanophores and xanthophores on head, trunk and tail at 500 μM as determined by photographic analysis. Whereas N-phenylthiourea (PTU) as a pigment inhibitor did not inhibit development of yellow pigments. Colorimetric detection of melanin further confirmed these results. Quantitative real time polymerase chain reaction (qRT-PCR) measurements indicated that genes (dct, slc24a5, tyr, tyrp1a, tyrp1b, silva) associated with the melanogenesis pathway were dramatically down-regulated following exposure to 500 μM DIYA. In addition, enzymatic activity of tyrosinase (TYR) decreased, also demonstrating that the underlying mechanism of hypopigmentation was attributed to the disruption of melanogenesis pathway. Transcription levels of xanthophore genes (gch2, bnc2, csf1a, csf1b, pax7a and pax7b) were also monitored by qRT-PCR assay. DIYA exposure up-regulated expression of gch2 and bnc2, but not csf1 and pax7. Tested DIYA analogues, brominated tyrosine was unlikely to inhibit pigmentation, indicating that the iodine substitution and dipeptides structure are of important structural feature for the inhibition of pigmentation. In this study, we observed that DIYA inhibited melanogenesis related genes, which might contribute to pigmentation defects. Moreover, as an emerging I-DBPs, the developmental toxicity of aromatic dipeptides should be further studied.



中文翻译:

评价新兴的消毒副产物3,5-di-I-酪氨酰丙氨酸引起的斑马鱼的色素沉着不足。

在对纯净水进行氯化处理之后,卤代二肽3,5-二-I-酪氨酰丙氨酸(DIYA)被确定为新型消毒副产物(DBP)。但是,对其毒性了解甚少。斑马鱼胚胎用于评估新型碘化DBP(I-DBP)的毒性。尽管DIYA对胚胎斑马鱼没有表现出很高的急性毒性(LC 50 > 2 mM),但通过照相分析确定,它显着抑制了头,躯干和尾巴上黑色素和黑色素的色素沉着(500μM)。而作为颜料抑制剂的N-苯基硫脲(PTU)不会抑制黄色颜料的显影。黑色素的比色检测进一步证实了这些结果。实时定量聚合酶链反应(qRT-PCR)测量表明,基因(dct,与黑色素生成途径相关的slc24a5tyrtyrp1atyrp1bsilva)在暴露于500μMDIYA后显着下调。此外,酪氨酸酶(TYR)的酶活性下降,也表明色素沉着不足的潜在机制是由于黑色素生成途径的破坏。还通过qRT-PCR测定法监测了黄体电泳基因(gch2bnc2csf1acsf1bpax7apax7b)的转录水平。DIYA暴露上调了gch2bnc2的表达,而不是csf1pax7。经过测试的DIYA类似物,溴化酪氨酸不太可能抑制色素沉着,表明碘取代和二肽结构对于抑制色素沉着具有重要的结构特征。在这项研究中,我们观察到DIYA抑制了黑色素生成相关基因,这可能导致色素沉着缺陷。此外,作为新兴的I-DBPs,芳香二肽的发育毒性应进一步研究。

更新日期:2020-07-03
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