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

Hydrogen sulfide (H₂S) is an environmental toxicant of significant health concern. The brain is a major target in acute H₂S poisoning. This study was conducted to test the hypothesis that acute and subchronic ambient H₂S exposures alter the brain metabolome. Male 7-8-week-old C57BL/6J mice were exposed by whole-body inhalation to 1000 ppm H₂S for 45 min and euthanized at 5 min or 72 h for acute exposure. For subchronic study, mice were exposed to 5 ppm H₂S 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 H₂S exposures matched with those of cerebral spinal fluid from patients with seizures or Alzheimer's disease. Acute H₂S exposure decreased excitatory neurotransmitters, aspartate, and glutamate, while the inhibitory neurotransmitter, serotonin, was increased. Branched-chain amino acids and glucose were increased by acute H₂S exposure. Subchronic H₂S exposure within OSHA guidelines surprisingly decreased serotonin concentration. In subchronic H₂S 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 H₂S poisoning and show that H₂S alters brainstem metabolome.