Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

Abstract

Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10 mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8 % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3 days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients.FigureArsenic species and temporal profiles over three days from nine patients

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

“…Although the methylated species are the primary products excreted in urine, their trivalent forms (i.e., MMA III and DMA III ) are intrinsically more toxic than As III , with the pentavalent species themselves being generally nontoxic at experimental levels relevant to human environmental exposure (Aposhian et al, 2003). Notably, arsenic trioxide (As 2 O 3 ) is used clinically as a highly effective treatment of acute promyelocytic leukemia and is converted to As III and, subsequently, to methylated species in vivo after administration (Chen et al, 2013).…”

Excretion patterns of arsenic and its metabolites in human saliva and urine after ingestion of Chinese seaweed

“…In a different study, Chen et al [27] analysed the arsenic speciation in the saliva of acute promyelocytic leukaemia (APL) patients undergoing arsenic trioxide treatment and suggested that saliva could be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients. However, all of the previous studies mainly focused on the detection of arsenic and its species in the saliva of humans exposed to inorganic arsenicals.…”

Identification of Methylated Dithioarsenicals in the Urine of Rats Fed with Sodium Arsenite

“…Moreover, arsenicals excreted via enterohepatic circulation might be transformed by gastrointestinal microbiota into thiolated arsenicals, which were then absorbed into the bloodstream and finally excreted into the urine . However, microbial production was not considered as the only source of thio-containing arsenicals because these arsenicals were also found in the liver of rats that received portal intravenous injection of DMA V , DMA III , MMA V , or MMA III , and in the saliva of acute promyelocytic leukemia patients undertaking intravenous infusion of iAs III . , The conversion of DMMTA V into DMDTA V was also observed in the incubation with rat RBCs . These results implied that some biological reactions in the organisms also could contribute to the formation of thio-containing arsenicals.…”

“…An Agilent 1100 series HPLC system that comprised a pump, degasser, autosampler, column temperature control, and reversed-phase C18 column (ODS-3, 150 mm × 4.6 mm, 3-μm particle size; Phenomenex, Torrance, CA, USA) was used for the separation of arsenicals. 27 An octadecylsilane guard cartridge (4 mm × 3 mm) was mounted before the analytical column. The mobile phase consisted of 5 mM tetrabutylammonium, 5% methanol, and 3 mM malonic acid (pH 5.65).…”

“…Recently, thio-containing methylated arsenicals have also been identified in various biological samples. − Dimethylmonothioarsinic acid (DMMTA V ) and dimethyldithioarsinic acid (DMDTA V ) were detected in human urine and blood samples from people who were exposed to arsenic via different pathways. − In animal studies, monomethylmonothioarsonic acid (MMMTA V ), DMMTA V , and DMDTA V were found in hamster urine, and MMMTA V and DMMTA V were found in rat urine and blood. − Nevertheless, the knowledge on where and how these thio-containing arsenicals are produced in the organisms is limited. Incubation of arsenicals (iAs V , DMA V , and trimethylarsine oxide (TMAO V )) with anaerobic microflora in mouse cecum can lead to the formation of thio-containing arsenicals. − Thioarsenicals were also formed from the incubation of human colon microbiota with inorganic arsenic or with arsenic-contaminated urban soils .…”