Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 21 December 2023 / Approved: 22 December 2023 / Online: 22 December 2023 (14:35:52 CET)

A peer-reviewed article of this Preprint also exists.

Kim, D.-S.; Santana Maldonado, C.M.; Giulivi, C.; Rumbeiha, W.K. Metabolomic Signatures of Brainstem in Mice following Acute and Chronic Hydrogen Sulfide Exposure. Metabolites 2024, 14, 53. Kim, D.-S.; Santana Maldonado, C.M.; Giulivi, C.; Rumbeiha, W.K. Metabolomic Signatures of Brainstem in Mice following Acute and Chronic Hydrogen Sulfide Exposure. Metabolites 2024, 14, 53.

Abstract

Hydrogen sulfide (H2S) is an environmental toxicant of health concern. The brain is a major target in acute H2S poisoning. This study was 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. The brainstem was removed for metabolomic analysis. Enrichment analysis showed 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, which may explain H2S-induced loss of consciousness. Branched-chain amino acids and glucose were increased by acute H2S exposure. Subchronic H2S exposure within OSHA guideline surprisingly decreased serotonin altering central nervous system. In subchronic H2S exposure, glucose was decreased while polyunsaturated fatty acids, inosine, and hypoxanthine were increased. Collectively, these results provide important mechanistic clues of acute and subchronic ambient H2S poisonings and show that H2S alters brainstem metabolome.

Keywords

Hydrogen sulfide; Metabolomics; Brainstem; Brain; Metabolism; Biomarkers; Neurotransmitters; Branched-chain amino acids; Polyunsaturated fatty acids

Subject

Biology and Life Sciences, Toxicology

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