AI Article Synopsis
- Arsenic trioxide (ATO) is commonly used to treat acute promyelocytic leukemia (APL), and a study was conducted to investigate its metabolism and toxicity in the red blood cells (RBCs) of APL patients.
- Nine APL patients received ATO through an 18-hour infusion, and blood samples were collected for analysis, revealing that inorganic arsenic (iAs) and its metabolites accumulated steadily in the RBCs during the treatment period.
- The findings highlighted that iAs was the most prevalent arsenic species in RBCs, with monomethylarsonic acid (MMA) being the dominant metabolite; importantly, the concentrations of these species were significantly higher in
Article Abstract
Background: Arsenic trioxide (ATO) is widely applied to treat acute promyelocytic leukemia (APL). To elucidate metabolism and toxicity of arsenic, we analyzed time course of arsenic species in red blood cells (RBCs) of APL patients.
Methods: Nine APL patients received ATO (0.16 mg/kg/day) through 18-h infusion. Blood was collected before daily administration (days 2 to 9), and at different time points on day 8. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were detected by HPLC-ICP-MS.
Results: Arsenic species reached C at 18 h on day 8. Arsenicals gradually accumulated during days 2 to 9, whereas their percentages remained almost constant. The general trend in red blood cells (RBCs) was iAs > MMA > DMA. MMA was consistently the predominant methylated arsenic metabolite in RBCs. iAs, MMA, and tAs (tAs = iAs + DMA + MMA) concentrations (P < 0.0001), MMA/DMA ratios (P = 0.0016) and iAs% (P = 0.0013) were higher in RBCs than in plasma.
Conclusions: Time course of arsenic species reveal kinetic characteristic of ATO metabolites in RBCs. Arsenic species accumulated with administration frequency. Arsenic species in RBCs were remarkably different from those in plasma. Time course of arsenic species in RBCs is important in ATO clinical application.
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| http://dx.doi.org/10.1080/17512433.2019.1586532 | DOI Listing |
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