cth-2/mpst-1-dependent H2S deficiency enhances acrylonitrile acute toxicity in Caenorhabditis elegans.

Acrylonitrile (AN) is a toxic, colorless to pale-yellow liquid extensively used in industrial production, has been linked to neurotoxicity. Though our previous study showed a correlation between AN-induced neurotoxicity and gasotransmitter hydrogen sulfide (H₂S) in mammalian cells, experimental evidence on overall animal toxicity and specific neurological injury is still limited. We aimed to further explore the molecular association between H₂S and AN-induced acute toxicity in Caenorhabditis elegans (C. elegans) by using its genetic advantages, and provide experimental evidence for the validation of H₂S donors as AN antidote. In the present study, we demonstrated that acute AN exposure resulted in toxicity as evidenced by changes in death rate, locomotor behavior, brood size, dopaminergic neuron morphology, and oxidative stress. Notably, AN inhibited the H₂S content, which was double-examined by methylene blue spectrophotometry and lead acetate paper assay. Furthermore, AN significantly decreased 3-mercaptopyruvate transferase (3-MPST)-mediated H₂S synthesizing activity and the transcription level of the corresponding coding gene mpst-1 but had no effect on the cystathionine β synthetase (CBS)/cystathionine γ lyase (CSE)-mediated H₂S synthesizing activity using L-cysteine as a common substrate and the mRNA levels of H₂S oxidative metabolism enzymes. cth-2 and mpst-1 mutations significantly downregulated the H₂S content and the corresponding H₂S synthesizing activity, and further enhanced the AN-induced toxicity response including lethality, brood size and lifespan. In contrast, H₂S donor GYY4137 significantly attenuated the AN-damaged survival rate, body bends, and dopaminergic neuron morphology. Our findings demonstrated that the reduction of H₂S mediates the acute toxicity of acrylonitrile.