Abstract
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.