Zinc chloride-induced TRPA1 activation does not contribute to toxicity in vitro

The hygroscopic zinc chloride (ZnCl₂) is often used to generate smoke screens. Severe adverse pulmonary health effects have been associated with inhalation of ZnCl₂ smokes. The underlying molecular toxicology is not known. Recent studies have shown that the Transient Receptor Potential Channel A1 (TRPA1) is important for sensing toxic chemicals. TRPA1 was shown to be activated by Zn²⁺ which was linked to pain and inflammation. In the present study, we investigated whether TRPA1 activation contributes to ZnCl₂-mediated toxicity in vitro. HEK wildtype (HEK-wt), TRPA1 overexpressing HEK (HEK-A1) and A549 lung cells, endogenously expressing TRPA1, were exposed to ZnCl₂. Changes of intracellular calcium levels [Ca²⁺]_i and cell viability were assessed after ZnCl₂ exposure in all cell types, without or with TRPA1 inhibition. ZnCl₂ increased [Ca²⁺]_i through TRPA1 channels in a complex manner in both HEK-A1 and A549 cells while HEK-wt did not respond to ZnCl₂. There was no difference in toxicity between HEK-wt and HEK-A1 cells after ZnCl₂ exposure. Inhibition of TRPA1 did not influence toxicity in all investigated cells. Thus, our in vitro results support the assumption that TRPA1 does not primarily mediate toxicity of ZnCl₂ and does probably not represent a therapeutic target to abate ZnCl₂ toxicity.