Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice

Kato, Koichi; Yamanaka, Kazuhiro; Shimoda, Yasuyo; Yamano, Yuko; Nagano, Kasuke; Hata, Akihisa; Endo, Yuichi; Tachikawa, Mariko; Endo, Ginji

doi:10.2131/jts.39.301

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…The early symptoms of arsine gas toxicity are vomiting, tachycardia, chest pain, headache, fever, and renal failure. Almost 25% of fatal exposure cases reported are due to hemolysis of red blood cells and subsequent kidney failure (Kato et al, 2014 ). The molecular mechanism underlying severe arsine toxicity is not completely understood.…”

Section: Arsenicals As Chemical Warfare Agentsmentioning

confidence: 99%

“…The molecular mechanism underlying severe arsine toxicity is not completely understood. Studies with hairless mice demonstrated that arsine is not absorbed through skin and therefore inhalation remains the major mode of arsine exposure (Kato et al, 2014 ). Acute arsine poisoning leads to serious oxidative damage to red blood cells by generating hydrogen peroxide and oxyhemoglobin adducts.…”

Section: Arsenicals As Chemical Warfare Agentsmentioning

confidence: 99%

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Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

et al. 2022

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Worldwide, more than 200 million people are estimated to be exposed to unsafe levels of arsenic. Chronic exposure to unsafe levels of groundwater arsenic is responsible for multiple human disorders, including dermal, cardiovascular, neurological, pulmonary, renal, and metabolic conditions. Consumption of rice and seafood (where high levels of arsenic are accumulated) is also responsible for human exposure to arsenic. The toxicity of arsenic compounds varies greatly and may depend on their chemical form, solubility, and concentration. Surprisingly, synthetic organoarsenicals are extremely toxic molecules which created interest in their development as chemical warfare agents (CWAs) during World War I (WWI). Among these CWAs, adamsite, Clark I, Clark II, and lewisite are of critical importance, as stockpiles of these agents still exist worldwide. In addition, unused WWII weaponized arsenicals discarded in water bodies or buried in many parts of the world continue to pose a serious threat to the environment and human health. Metabolic inhibition, oxidative stress, genotoxicity, and epigenetic alterations including micro-RNA-dependent regulation are some of the underlying mechanisms of arsenic toxicity. Mechanistic understanding of the toxicity of organoarsenicals is also critical for the development of effective therapeutic interventions. This review provides comprehensive details and a critical assessment of recently published data on various chemical forms of arsenic, their exposure, and implications on human and environmental health. Graphical abstract

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Section: Arsenicals As Chemical Warfare Agentsmentioning

confidence: 99%

Section: Arsenicals As Chemical Warfare Agentsmentioning

confidence: 99%

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

et al. 2022

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“…and metalloids. Such studies published these past three years in the Journal of Toxicological Sciences investigated the toxicity of many types of metals, including cadmium (Ohtani et al, 2013;Miura et al, 2013;Baba et al, 2014;Du et al, 2014;Park et al, 2015;Lukkhananan et al, 2015), mercury (Yoshida et al, 2013;Kim et al, 2014), methylmercury (Hwang et al, 2013a(Hwang et al, , 2013bIwai-Shimada et al, 2013;Chang et al, 2013;Hirooka et al, 2013;Kim et al, 2013;Watanabe et al, 2013;Shao et al, 2015;Toyama et al, 2015), aluminum (Zhang et al, 2013;Jinzhu et al, 2015), manganese (Fujishiro et al, 2013), uranium (Lestaevel et al, 2013), arsenic (Tokumoto et al, 2013;Wang et al, 2015), arsine (Kato et al, 2014), organic bismuth (Kohri et al, 2015), chromium (Kimura et al, 2015), and tributyltin (Oyanagi et al, 2015). Although methylmercury is one of the organic-inorganic hybrid molecules (the minimum unit!…”

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confidence: 99%

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

2016

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Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

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“…Blood samples exposed to arsine in vivo were obtained in a previous study 10) . Briefly, male Hos: HR-1 hairless mice were placed in an acrylic exposure chamber and exposed to 2.5 l of arsine gas for 5 minutes under isoflurane anesthesia.…”

Section: Sample Preparationmentioning

confidence: 99%

“…Recent reports have described an unidentified arsenic compound derived from blood cells with a molecular weight over 10,000 after in vitro exposure of blood to arsine 9) . Furthermore, it was indicated that the arsenic coexisted with hemoglobin in red blood cells separated from mice exposed to arsine 10) . The aim of this study was to identify an arsenic adduct that can serve as a candidate biomarker in both plasma separated from preserved mouse blood exposed to arsine in vitro and plasma from mice exposed to arsine in vivo.…”

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Possible production of arsenic hemoglobin adducts via exposure to arsine

Yamauchi¹,

Yamano

Yamanaka

et al. 2015

Journal of Occupational Health

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Possible production of arsenic hemoglobin adducts via exposure to arsine: Takenori YAMAU‐CHI, et al. Department of Public Health Faculty of Medicine, University of Miyazaki Objective Arsine is an arsenic compound generated as a by‐product in metal refineries. Accidental poisoning occurs sporadically; however, the administrative level for workers has not been established. Thus, it is essential to identify a highly specific biomarker for risk management in the workplace. The aim of this study was to identify an arsenic adduct, a potential biomarker, in the plasma. Methods Preserved mouse blood was exposed to arsine in vitro, and the plasma was separated. The residual clot of the control sample was hemolyzed using ultrapure water, and the supernatant was collected. Plasma from mice exposed to arsine in vivo was also separated from blood. Immunoprecipitation assays were conducted using all samples after ultrafiltration, and three fractions were collected. The total arsenic concentration in each fraction was quantified using inductively coupled plasma mass spectrometry (ICP‐MS). The three in vitro samples and the eluate fraction from immunoprecipitation were analyzed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). Results In the exposed samples, the arsenic concentration in the fraction containing immunocomplexes was higher when immunoprecipitation was conducted with an anti‐globin antibody. Three peaks were specifically observed in arsine‐exposed samples after MALDI‐TOF‐MS analysis. Two of them were around m/z 15,000, and the other was m/z 15,700. The latter peak was confirmed even after immunoprecipitation. Conclusions Globin forms an adduct with arsenic after both in vitro and in vivo exposure to arsine. This adduct together with hemoglobinuria could be a candidate biomarker of acute arsine poisoning in plasma.

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Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice

Cited by 10 publications

References 19 publications

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

Possible production of arsenic hemoglobin adducts via exposure to arsine

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