Metabolomic Signatures of Brainstem in Mice following Acute and Subchronic Hydrogen Sulfide Exposure.

Hydrogen sulfide (HS) is an environmental toxicant of significant health concern. The brain is a major target in acute HS poisoning. This study was conducted to test the hypothesis that acute and subchronic ambient HS exposures alter the brain metabolome. Male 7-8-week-old C57BL/6J mice were exposed by whole-body inhalation to 1000 ppm HS for 45 min and euthanized at 5 min or 72 h for acute exposure. For subchronic study, mice were exposed to 5 ppm HS 2 h/day, 5 days/week for 5 weeks. Control mice were exposed to room air. The brainstem was removed for metabolomic analysis. Enrichment analysis showed that the metabolomic profiles in acute and subchronic HS exposures matched with those of cerebral spinal fluid from patients with seizures or Alzheimer's disease. Acute HS exposure decreased excitatory neurotransmitters, aspartate, and glutamate, while the inhibitory neurotransmitter, serotonin, was increased. Branched-chain amino acids and glucose were increased by acute HS exposure. Subchronic HS exposure within OSHA guidelines surprisingly decreased serotonin concentration. In subchronic HS exposure, glucose was decreased, while polyunsaturated fatty acids, inosine, and hypoxanthine were increased. Collectively, these results provide important mechanistic clues for acute and subchronic ambient HS poisoning and show that HS alters brainstem metabolome.