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

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