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Understanding the Pulmonary Effects of Inhaled Arsenic Trioxide (ATO)

Arsenic trioxide (ATO) is an inorganic arsenical that poses significant environmental and public health risks due to its toxic nature. While it is widely used in various industrial and medicinal applications, the potential harm caused by intentional or accidental exposure cannot be overlooked. Despite its prevalence, the pulmonary pathology resulting from acute high-dose exposure to ATO has not been extensively studied. In this blog post, we will explore a murine model developed to investigate the effects of a single inhaled exposure to ATO and its implications on pulmonary function.

ATO-Induced Hypoxemia and Alveolar-Capillary Membrane Disruption

Following the inhalation of ATO, arterial blood-gas measurements revealed the development of hypoxemia, indicating a decrease in oxygen levels. This finding suggests that ATO inhalation interferes with the normal gas exchange process within the lungs. Further examination of bronchoalveolar lavage fluid (BALF) supernatant showed an increase in total protein and IgM, indicating disruption of the alveolar-capillary membrane. Additionally, the onset of pulmonary edema was observed, suggesting an abnormal accumulation of fluid in the lungs.

Inflammatory Response and Immune Dysregulation

Analysis of the BALF from ATO-exposed mice demonstrated elevated levels of HMGB1, a damage-associated molecular pattern (DAMP) molecule, which indicates cellular damage and inflammation. Differential cell counts revealed an increase in neutrophils, a type of white blood cell associated with inflammation and immune responses. The BALF supernatant also exhibited elevated levels of eotaxin/CCL-11 and MCP-3/CCL-7 proteins, known to attract specific immune cells. Interestingly, there was a reduction in the levels of anti-inflammatory cytokines IL-10 and IL-19, as well as IFN-γ and IL-2. This dysregulation suggests an inflammatory environment with impaired immune responses in the lungs of ATO-exposed mice.

Lung Inflammation and Molecular Signaling

Further examination of the lung tissue from ATO-exposed mice revealed increased levels of G-CSF, CXCL-5, and CCL-11 proteins. These molecules are associated with neutrophil recruitment and activation, exacerbating the inflammatory response. Increased mRNA levels of TNF-a and CCL2 in the ATO-challenged lungs further supported the presence of inflammation. Collectively, these findings indicate that ATO inhalation triggers an inflammatory cascade in the lungs, promoting tissue damage and dysfunction.

Impact on Pulmonary Function

To assess the impact of ATO exposure on pulmonary function, researchers the precision flexiVent system. The results demonstrated a significant increase in respiratory and lung elastance in ATO-exposed mice, consistent with an acute lung injury phenotype. Pressure-volume loops exhibited a downward shift and a decrease in inspiratory capacity, indicating reduced lung compliance. Furthermore, flow-volume curves displayed a decrease in forced expiratory volume at 0.1 second (FEV0.1) and forced expiratory flow at 50% of forced vital capacity (FEF50). These functional alterations closely resemble the characteristics of acute respiratory distress syndrome (ARDS) in humans.


The murine model developed to study the effects of inhaled ATO exposure has shed light on the pulmonary pathology induced by this toxic compound. The research findings demonstrate that ATO inhalation leads to significant pulmonary damage, disruption of the alveolar-capillary membrane, immune dysregulation, and an inflammatory response resembling ARDS. Understanding the mechanisms underlying ATO-induced lung injury is crucial for developing preventive measures and therapeutic interventions to mitigate the risks associated with this environmental contaminant and occupational hazard. Further studies are warranted to explore potential treatment strategies and long-term consequences of ATO exposure in humans.


Pulmonary pathogenesis in a murine model of inhaled arsenical exposure. (2023). Mariappan, N., et al. Archives of Toxicology, 97: 1847-1858

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