Kittler Katrin, Hurtaud-Pessel Dominique, Maul Ronald, Kolrep Franziska, Fessard Valérie
ANSES, French Agency for Food, Environmental and Occupational Health Safety, Fougères Laboratory, 10B rue Claude Bourgelat - Javené, CS 40608, 35306, Fougères Cedex, France; Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Straße 11, 12489, Berlin, Germany.
ANSES, French Agency for Food, Environmental and Occupational Health Safety, Fougères Laboratory, 10B rue Claude Bourgelat - Javené, CS 40608, 35306, Fougères Cedex, France.
Toxicon. 2016 Feb;110:47-50. doi: 10.1016/j.toxicon.2015.11.007. Epub 2015 Dec 2.
No evidence for phase I metabolites of the cyanotoxin cylindrospermopsin (CYN) was given using HepaRG cells and different liver tissue fractions when studying metabolic conversion. Although the application of ketoconazole, a CYP3A4 inhibitor, led to a decreased cytotoxicity of CYN, no metabolites were detected applying high resolution mass spectrometry. Quantification of non-modified CYN led to recovery rates of almost 100%. Consequently, reduction of CYN toxicity in the presence of metabolism inhibiting agents must be attributed to alternative pathways.
在研究代谢转化时,使用HepaRG细胞和不同肝脏组织组分未发现蓝藻毒素柱孢藻毒素(CYN)的I相代谢产物。尽管应用细胞色素P450 3A4(CYP3A4)抑制剂酮康唑可降低CYN的细胞毒性,但应用高分辨率质谱未检测到代谢产物。未修饰CYN的定量分析得出回收率几乎为100%。因此,在存在代谢抑制剂的情况下CYN毒性的降低必定归因于其他途径。