Speciation analysis of arsenic in urine samples from APL patients treated with single agent As2O3 by HPLC-HG-AFS

Guo, Meihua; Li, Jing; Fan, Shengjin; Liu, Wensheng; Wang, Bin; Gao, Chunlu; Zhou, Jin; Hai, Xin

doi:10.1016/j.jpba.2019.04.014

Cited by 15 publications

(7 citation statements)

References 19 publications

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“…Published reports and our preliminary results suggested that ATO is biotransformed into two types of major metabolites through oxidative methylation in human: MMA and DMA, which is catalyzed by arsenic methyltransferase ( 10 , 11 , 16 , 17 ). As V is a rare metabolite in the process ( 16 ).…”

Section: Discussionmentioning

confidence: 60%

“…The prototype drug As III and its metabolites are widely distributed throughout the body. The arsenic species can be detected in urine ( 11 ), plasma ( 16 ), red blood cells ( 17 ), leukocytes ( 37 ), granulocytes ( 37 ), and cerebrospinal fluid (CSF) ( 38 ) of APL patients treated with ATO, and in kidney ( 39 ), liver ( 39 ), and heart ( 39 ) of rat treated with ATO. In this study, the C trough , percentage, and methylation index of arsenic species in plasma from pregnant and non-pregnant women treated with ATO were evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…All samples were immediately frozen at −80°C until analysis. The analysis of arsenic species in AF and plasma was performed by HPLC–HG–AFS (LC-AFS 6500, Beijing Haiguang Instruments Co., Ltd., China) ( 11 , 16 ). The concentrations of arsenic compounds were expressed as the concentrations of the arsenic element (As).…”

Section: Methodsmentioning

confidence: 99%

“…Arsenic can be metabolized from inorganic arsenic [iAs, arsenite (As III ) and arsenate (As V )] to monomethylated arsenic (MMA, consists of MMA III and MMA V ) and dimethylated arsenic (DMA, consists of DMA III and DMA V ) by a sequence of reductions and oxidative methylations ( 10 – 12 ). As III and As V undergo interconversion through natural oxidation and reduction by arsenate reductase ( 10 , 11 ). The toxicities of different arsenic compounds vary and depend on their valency and concentration ( 10 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Arsenic Trioxide Therapy During Pregnancy: ATO and Its Metabolites in Maternal Blood and Amniotic Fluid of Acute Promyelocytic Leukemia Patients

Guo

Chen

et al. 2022

Front. Oncol.

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Acute promyelocytic leukemia (APL) is extremely fatal if treatment is delayed. Management of APL in pregnancy is a challenging situation. Arsenic trioxide (ATO) is successfully applied to treat APL. ATO can be transformed into different arsenic species [arsenite (AsIII), monomethylated arsenic (MMA, consists of MMAIII and MMAV), dimethylated arsenic (DMA, consists of DMAIII and DMAV), and arsenate (AsV)], which produce different toxic effects. Investigating the maternal and fetal exposure to arsenic species is critical in terms of assessing maternal and fetal outcomes, choice of optimal treatment, and making decisions for attempting to preserve the obstetrical and fetal wellbeing. In this study, maternal blood and amniotic fluid (AF) from APL patients treated with ATO in pregnancy and blood samples of non-pregnant patients were collected. Concentrations of inorganic arsenic (iAs, iAs = AsIII+AsV), MMA, and DMA were analyzed by high-performance liquid chromatography–hydride generation–atomic fluorescence spectrometry (HPLC–HG–AFS). The difference in arsenic species of plasma between pregnant patients and non-pregnant patients, distribution of arsenic compounds in AF and maternal plasma, and arsenic penetration into AF were explored. The outcomes of pregnant women treated with ATO and their fetus were analyzed. No significant differences in arsenic concentration, percentage, and methylation index [PMI: primary methylation index (MMA/iAs); SMI: secondary methylation index (DMA/MMA)] between pregnant women and non-pregnant women (p > 0.05) were observed. The mean ratios of AF to maternal plasma were as follows: iAs, 2.09; DMA, 1.04; MMA, 0.49; and tAs, 0.98. Abortion rate is higher with the diagnosis at an earlier gestational age, with 0%, 67%, and 100% of pregnancies ending in abortion during the third, second, and first trimester, respectively. The age of the pregnant women, the dose of ATO, and the duration of fetal exposure in utero had no influence on fetal outcomes. All APL women achieved complete remission (CR). Collectively, ATO and its metabolites can easily cross the placenta. Levels and distribution of arsenic species in maternal plasma and AF gave evidence that arsenic species had a different ability to penetrate the placenta into AF (iAs > DMA > MMA) and indicated a relatively high fetal exposure to ATO and its metabolites in utero. Gestational age at diagnosis was more likely to be closely related to fetal outcomes, but had no effects on mother outcomes.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arsenic Trioxide Therapy During Pregnancy: ATO and Its Metabolites in Maternal Blood and Amniotic Fluid of Acute Promyelocytic Leukemia Patients

Guo

Chen

et al. 2022

Front. Oncol.

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“…The As speciations in urine was determined by high performance liquid chromatography-hydride generation-atomic uorescence spectrometry (HPLC-HG-AFS) according to the method from Guo et al (Guo and Li et al 2019). The EClassical 3100 High E ciency Liquid Phase Separation System (Dalian Elite Analytical Instruments Co., Ltd.) with PRP-X100 anion exchange chromatography column (250.0 mm × 4.1 mm × 10.0 µm, Hamilton, Switzerland) was used to separate different As speciations, AFS-8530 atomic uorescence spectrophotometer (Beijing Haiguang Instrument Co., Ltd.) was used to quantify the four As speciations.…”

Section: As Speciations Determinationmentioning

confidence: 99%

Influencing Trend and Extent of Combined Exposure Levels of Total Arsenic and Inorganic Arsenic on Arsenic Methylation Capacity Among University Students: Findings from Bayesian Analysis Using Kernel Machine Regression

Jiang

Zhang

et al. 2021

Preprint

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The arsenic (As) methylation capacity is an important determinant of the susceptibility to arsenic-related diseases. Total As (TAs) or inorganic As (iAs) was reported to associate with As methylation capacity individually, however, influencing trend and extent of their combined exposure levels on methylation capacity remains poorly understood. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids using HPLC-HG-AFS, and calculated the primary (PMI: (MMA+DMA)/TAs) and secondary (SMI: DMA/(MMA+DMA)) methylation capacity indexes in 209 university students in Hefei, China, a non-As endemic area. Subjects were given with a standardized questionnaire to inquire their sociodemographic characteristics. Bayesian kernal machine regression (BKMR) analysis was used to estimate the association of lnTAs and lniAs levels with methylation indices (ln%MMA, ln%DMA, lnPMI, lnSMI). The median concentration of iAs, MMA and DMA was 1.22, 0.92 and 12.17 μg/L, respectively; the proportions of iAs, MMA and DMA were 8.76%, 6.13% and 84.84%, respectively. Females had higher %DMA and lower %MMA, while males had lower %DMA and higher %MMA. The combined levels of lnTAs and lniAs showed monotonic decrease in change of ln%DMA and lnSMI other than ln%MMA, additionally, change in ln%PMI was decreased only when levels of lnTAs and lniAs were larger than their 60th percentiles compared to they were at 50th percentile. With regard to single exposure level, the lnTAs showed positive correlation with ln%DMA, lnPMI, lnSMI when lniAs was set at a specific level; while lniAs showed negative correlation with ln%DMA, lnPMI, lnSMI when lnTAs was set at a specific level; and all the dose-response relationships were nonlinear. Our results suggested that combined levels of TAs and iAs played an important role in reducing As methylation capacity, expecially iAs; and the reduction only occured when TAs and iAs were up to a certain combined level.

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The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

Liao

Chen

Huang

et al. 2022

Cancer Chemother Pharmacol

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Speciation analysis of arsenic in urine samples from APL patients treated with single agent As2O3 by HPLC-HG-AFS

Cited by 15 publications

References 19 publications

Arsenic Trioxide Therapy During Pregnancy: ATO and Its Metabolites in Maternal Blood and Amniotic Fluid of Acute Promyelocytic Leukemia Patients

Arsenic Trioxide Therapy During Pregnancy: ATO and Its Metabolites in Maternal Blood and Amniotic Fluid of Acute Promyelocytic Leukemia Patients

Influencing Trend and Extent of Combined Exposure Levels of Total Arsenic and Inorganic Arsenic on Arsenic Methylation Capacity Among University Students: Findings from Bayesian Analysis Using Kernel Machine Regression

The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

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