Metabolism study for CUMYL-4CN-BINACA in human hepatocytes and authentic urine specimens: Free cyanide is formed during the main metabolic pathway

2018 ◽  
Vol 10 (8) ◽  
pp. 1270-1279 ◽  
Author(s):  
Anna Åstrand ◽  
Svante Vikingsson ◽  
Daniel Lindstedt ◽  
Gunilla Thelander ◽  
Henrik Gréen ◽  
...  
Author(s):  
Linyi Zhang ◽  
Chen Song ◽  
Yaoyao Xu ◽  
Yajun Shi ◽  
Xiaoling Liu

Abstract A single strain capable of efficient S2−-oxidizing was isolated from a black-odor river in Beijing. The single strain was identified as Stenotrophomonas through the physiology and biochemical characteristics as well as the 16S rRNA sequencing experiment. This strain was named as Stenotrophomonas sp.sp3 (strain sp3). The experimental results showed that for the strain sp3 growth and S2− oxidization, the optimal conditions were as follows: 25 °C of temperature, initial pH 7, 2.5 g/L of initial glucose concentration and 1.00 g/L of initial cell concentration. It was found that there were 31 kinds of sulfur oxidation related genes in the strain sp3 through the whole genomic analysis. The results of the transcriptome analysis suggested that the main metabolic pathway of S2− to SO42− was the paracoccus sulfur oxidation process. The bioconversion processes of S2− to S0, S2− to SO32−, S2O32− to S0 and SO32−, and SO32− to SO42− were controlled by hdrA, cysIJ, tst and sox gene, respectively.


2021 ◽  
Vol 8 ◽  
Author(s):  
Chong-Yin Huang ◽  
Ya-Jun Huang ◽  
Zhuo-Yi Zhang ◽  
Yi-Song Liu ◽  
Zhao-Ying Liu

Background:Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority.Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined.Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activityConclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats.


1990 ◽  
Vol 21 (3) ◽  
pp. 206-208
Author(s):  
S. Jerebzoff‐Quintin ◽  
S. Jerebzoff ◽  
R. Romestant

Author(s):  
Kayoko Minakata ◽  
Koutaro Hasegawa ◽  
Itaru Yamagishi ◽  
Hideki Nozawa ◽  
Masako Suzuki ◽  
...  

Abstract In this study, solid tissues such as the lung, liver, kidney and urine were highlighted to profile the AB-PINACA in vivo metabolites in a fatal abuse case, although such metabolite analysis is usually made with urine specimens. We compared the relative peak intensities of in vivo metabolites of AB-PINACA in lung, liver, kidney and urine specimens collected at the autopsy of its abuser with its in vitro metabolites in human hepatocytes. The metabolites of AB-PINACA in tissues were extracted after homogenization. The urine specimen and portions of the extracted metabolites from tissues were firstly hydrolyzed with β-glucuronidase, and the metabolites were extracted. For in vitro experiment, AB-PINACA was incubated with human hepatocytes for 3 h to produce its metabolites. The identification of the in vivo and in vitro metabolites was performed using liquid chromatography (LC)–high-resolution Orbitrap-tandem mass spectrometry (MS-MS), and the relative intensities of these metabolites were measured using low resolution LC–quadrupole-ion trap-MS-MS. Thirteen metabolites of AB-PINACA were characterized in vivo in several human specimens and in in vitro human hepatocytes. They were produced by the terminal amide hydrolysis to carboxylic acid, hydroxylation, carbonyl formation and/or glucuronidation. The most detectable metabolite in the hepatocytes, lung or liver was the one produced by the terminal amide hydrolysis, whereas the top metabolite in the kidney or urine was the one produced by hydroxylation or carbonyl formation on the pentyl side chain after the terminal amide hydrolysis, respectively. At least 12 metabolites of AB-PINACA were detected in authentic human lung, liver or kidney specimen from a cadaver. It is concluded that the postmortem metabolite profiling of AB-PINACA can be fulfilled with solid tissues, and the lung and kidney were most recommendable especially when urine specimen is not available.


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