Sub-acute dihydroxyacetone exposure alters mitochondria and induces cardiac strain

Dihydroxyacetone (DHA), a carbohydrate detected in e-cigarette aerosols and used in sunless tanning products, is genotoxic and cytotoxic in various cell models. We previously demonstrated that inhaled DHA induced lung injury in A/J mice. Here, we evaluated cardiac effects of sub-acute DHA exposure in A/J mice and human Ac16 cardiomyocytes. Two weeks of DHA exposure significantly increased cardiac mitochondrial DNA (mtDNA) copy number and altered global longitudinal strain in both sexes. Ejection fraction and fractional shortening did not differ significantly after DHA exposure in either sex, though male mice showed increased ejection fraction and fractional shortening, while female mice decreased in both parameters. Male DHA-exposed mice also showed decreased body weight, while female mice body weight was unchanged. Plasma metabolic analyses, limited to female mice due to Flexivent analysis on the males, revealed significantly altered metabolic markers, including increased glucose levels and decreased resistin. To confirm mitochondrial DNA changes and DNA damage induction, we examined DHA exposure in the Ac16 cells sub-acutely exposed to DHA for 14 days. Sub-acute DHA exposure increased oxidative DNA lesions, without a significant increase in reactive oxygen species or mitochondrial content. mtDNA copy number was also increased in the sub-acutely exposed Ac16 cells. These results demonstrate that inhaled DHA alters cardiac cells and induces early cardiac tissue and cell changes, in addition to its lung effects, suggesting that the e-liquid oxidation products pose inhalation-related health risks.