Detection of diphenylarsinic acid and its derivatives in human serum and cerebrospinal fluid

Ishii, Kazuhiro; Itoh, Yasunori; Iwasaki, Naoko; Shibata, Yasuyuki; Tamaoka, Akira

doi:10.1016/j.cca.2014.01.029

Cited by 11 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S2). The first symptomatic case was recognized in 2000, suggesting that the DPAA concentration in well water reached the lowest‐observed adverse‐effect level at that time . Another limitation of this study is that nuclear SPECT suffers from a low spatial resolution.…”

Section: Discussionmentioning

confidence: 94%

“…A 20‐μL aliquot was then injected into a high‐performance liquid chromatography system (Agilent 1100 series, Agilent Technologies, Santa Clara, CA, USA) equipped with an Asahipak GS‐220 7C column (7.6 × 100 mm, SHOWA DENKO K.K., Tokyo, Japan). The DPAA concentration was determined by inductively coupled plasma mass spectrometry (Agilent 7500, Agilent Technologies) as previously described .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication

Ishii

Nemoto

Iwasaki

et al. 2018

Euro J of Neurology

View full text Add to dashboard Cite

Background and purpose Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar–brainstem and temporo‐occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA‐contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single‐photon emission computed tomography (CBF‐SPECT). Methods The DPAA‐exposed inhabitants (n = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high‐performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF‐SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF‐SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects. Results Compared with control subjects, CBF in symptomatic DPAA‐exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF. Conclusion These data suggest that CBF‐SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication

Ishii

Nemoto

Iwasaki

et al. 2018

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…Previous experiments using rodents have shown that inorganic arsenic (iAs) can cross the blood–brain barrier (BBB; Rodríguez et al 2005; Juárez-Reyes et al 2009). Similarly to organic arsenic, DPAA was also detected in the CSF obtained from the residents of Kamisu who were exposed to DPAA (Ishii et al 2014). Their CSF/serum ratios of DPAA were 3.7 and 3.0% at the first and 14th days after their last exposure, respectively (Ishii et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly to organic arsenic, DPAA was also detected in the CSF obtained from the residents of Kamisu who were exposed to DPAA (Ishii et al 2014). Their CSF/serum ratios of DPAA were 3.7 and 3.0% at the first and 14th days after their last exposure, respectively (Ishii et al 2014). Consistent with these previous results, DPAA was detected in the CSF of cynomolgus monkeys in this study.…”

Section: Discussionmentioning

confidence: 99%

Long-term accumulation of diphenylarsinic acid in the central nervous system of cynomolgus monkeys

et al. 2017

Self Cite

View full text Add to dashboard Cite

Diphenylarsinic acid (DPAA) is an organic arsenic compound used for the synthesis of chemical weapons. We previously found that the residents of Kamisu city in Ibaraki Prefecture, Japan, were exposed to DPAA through contaminated well water in 2003. Although mounting evidence strongly suggests that their neurological symptoms were caused by DPAA, the dynamics of DPAA distribution and metabolism after ingestion by humans remain to be elucidated. To accurately predict the distribution of DPAA in the human body, we administrated DPAA (1.0 mg/kg/day) to cynomolgus monkeys (n = 28) for 28 days. The whole tissues from these monkeys were collected at 5, 29, 170, and 339 days after the last administration. The concentration of DPAA in these tissues was measured by liquid chromatography–mass spectrometry. We found that DPAA accumulated in the central nervous system tissues for a longer period than in other tissues. This finding would extend our knowledge on the distribution dynamics and metabolism of DPAA in primates, including humans. Furthermore, it may be useful for developing a treatment strategy for patients who are exposed to DPAA.

show abstract

“…The maximum exposed dose of the subjects in the Kamisu cohort who developed CNS symptoms was estimated to be 0.93 mg/kg/day (Ishii et al, 2014). The monkeys in our study were therefore administered 1.0 mg/kg/day of DPAA(V) orally according to the schedule shown in Fig.…”

Section: Histopathological Changes In the Hepatic Tissues Of Monkeys mentioning

confidence: 99%

Hepatic histopathological changes and dysfunction in primates following exposure to organic arsenic diphenylarsinic acid

et al. 2018

Self Cite

View full text Add to dashboard Cite

Organic arsenic diphenylarsinic acid (DPAA[V]) accumulates at high concentrations in the liver of primates after its subchronic administration. However, no studies on the hepatic effects of organic arsenic compounds, including DPAA(V), on primates have been reported to date. To clarify the toxicokinetics of DPAA(V) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of DPAA(V) for 28 days. Four histopathological changes in the specimens were observed and pathologically evaluated. Atypical ductular proliferation was found in the DPAA(V)-exposed liver throughout the period. Inflammatory cell infiltration in Glisson's capsules and lipid droplets were seen at earlier periods after administration. Conversely, inflammatory cell infiltration in liver lobules was seen later after administration. In this experiment, we did not confirm the hepatic dysfunction of DPAA(V)-exposed monkeys by blood chemistry tests. To compensate for this, we further investigated the blood from a patient who exhibited several neurological symptoms after DPAA(V) exposure. Her blood chemistry test values for aspartate transaminase, alanine transaminase, and lactate dehydrogenase were elevated, suggesting that her liver may have been damaged by DPAA(V) exposure. Together, these findings suggest that the accumulation of DPAA(V) may induce differential histopathological changes in primate hepatocytes, resulting in decreased liver function. This is the first report to investigate the liver of primates pathologically after exposure to organic arsenic DPAA(V). Our findings will help expand our knowledge regarding the effect of DPAA(V) on the liver of primates.

show abstract

Detection of diphenylarsinic acid and its derivatives in human serum and cerebrospinal fluid

Cited by 11 publications

References 13 publications

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication

Long-term accumulation of diphenylarsinic acid in the central nervous system of cynomolgus monkeys

Hepatic histopathological changes and dysfunction in primates following exposure to organic arsenic diphenylarsinic acid

Contact Info

Product

Resources

About