Inhalation exposure to dihydroxyacetone promotes lung injury and pulmonary fibrosis in A/J mice

Acute and sub-acute exposure to dihydroxyacetone (DHA), a compound found in e-cigarette aerosols and spray tanning products, was assessed for its impact on lung injury in A/J mice. Mice were exposed to inhaled DHA doses of 5, 130, and 600 µg and evaluated at 1 and 24 h post-exposure. Acute exposure to DHA led to significant inflammatory responses, indicated by increased bronchoalveolar lavage fluid (BALF) protein levels at 5, 130, and 600 µg and notably elevated inflammatory cytokines IL-6 and TNF-α 1 h post-exposure. 24 h post-exposure, the 130 and 600 µg doses showed elevated BALF cell counts. Histological analysis revealed significant alveolar damage and increased lung injury scores for the 130 and 600 µg doses. For sub-acute exposure, male and female mice were exposed to 5 µg DHA for 14 days. Increased BALF cell counts and protein levels were observed, with sex-specific differences in cytokine responses. Male mice exhibited reduced levels of IFN-γ and TNF-α, while female mice showed significant lung damage characterized by decreased alveolar density and increased collagen deposition indicative of fibrosis. Functional assessments showed mixed obstructive and restrictive lung changes. This study highlights DHA's potential to induce acute inflammatory responses and chronic lung damage, including both emphysematous and fibrotic changes. These findings suggest that DHA exposure, particularly from aerosolized e-liquids, could contribute to respiratory complications, underscoring the need for further research on long-term exposure effects.