Exceptions in patterns of arsenic compounds in urine of acute promyelocytic leukaemia patients treated with As2O3

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• 作者：Zdenka Šlejkovec ; Helena Podgornik ; Peter Černelč ; Ingrid Falnoga
• 关键词：Arsenic trioxide ; Acute promyelocytic leukemia ; Metabolites ; Urine ; Speciation ; Biotransformation
• 刊名：Biometals
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：29
• 期：1
• 页码：107-118
• 全文大小：860 KB
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• 作者单位：Zdenka Šlejkovec (1)
  Helena Podgornik (2)
  Peter Černelč (2)
  Ingrid Falnoga (1)
  
  1. Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia
  2. University Medical Centre Ljubljana, Zaloška 7, 1000, Ljubljana, Slovenia
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Physical Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1572-8773

文摘

Arsenic trioxide (As(III) in solution) has been shown to be the most active single agent in combating acute promyelocytic leukemia (APL). It is metabolized and excreted via urine as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V), along with excess As(III). In our study eight APL patients were treated (intravenously) with 0.15 mg As₂O₃/kg/day. During the therapy As(III) and its metabolites were followed in pre- and post-infusion urine using HPLC for separation followed by on-line detection using hydride generation-atomic fluorescence spectrometry. Five patients had a normal excretion pattern of residual arsenic compounds in morning pre-infusion urine, with 15–25 % of As(III), 35–55 % of DMA, 25–30 % of MMA and 1–5 % of As(V), while three patients showed unexpected exceptions from typical excretion patterns of arsenic compounds (i) a high DMA/MMA ratio (factor 5.3), (ii) severe As(III) oxidation (10.2 % As(III) converted to As(V)) or (iii) the presence of an excessive amount of As(III) (average 30.4 % of total arsenic). Intriguing was the occurrence of post-infusion oxidation of As(III) to As(V) observed in almost all patients and being especially high (>40 %) in patient with increased residual As(V). Results indicate that arsenic metabolites patterns can be unpredictable. Observed high levels of un-metabolised As(III) are a warning signal for side effects and for routine determination of arsenic metabolites during first days of treatment. High or low percentages of MMA or DMA did not show any observable effect on treatment results, while clear presence of post-infusion As(V) supports theoretical claims of in vivo oxidation (detoxification) of As(III) to As(V) associated with various metabolic processes. Keywords Arsenic trioxide Acute promyelocytic leukemia Metabolites Urine Speciation Biotransformation