Inhibition of ALDH2 protects PC12 cells against formaldehyde‐induced cytotoxicity: involving the protection of hydrogen sulphide

Summary Formaldehyde ( FA ), a common environmental contaminant, has toxic effects on the central nervous system ( CNS ). We have previously found that hydrogen sulphide (H 2 S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA . However, the underlying mechanism is poor. Aldehyde‐dehydrogenase‐2 ( ALDH 2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H 2 S antagonizes FA ‐induced neurotoxicity by modulating ALDH 2. In the present study, we found that the exposure of PC 12 cells to FA causes increase in ALDH 2 expression and activity. Daidzin, an inhibitor of ALDH 2, significantly antagonizes FA ‐exerted cytotoxicity and oxidative stress including the accumulation of intracellular reactive oxygen species ( ROS ), 4‐hydroxy‐2‐trans‐nonenal (4‐ HNE ), and malondialdehyde ( MDA ), in PC12 cells. We also showed that daidzin markedly attenuated FA ‐induced apoptosis in PC12 cells. Furthermore, we found that H 2 S reverses FA ‐elicited upregulation of ALDH 2 in PC 12 cells. Our results demonstrated the involvement of downregulation of ALDH 2 in the protection of H 2 S against FA neurotoxicity.