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Acute hydrogen sulfide-induced neurochemical and morphological changes in the brainstem
Journal article   Open access   Peer reviewed

Acute hydrogen sulfide-induced neurochemical and morphological changes in the brainstem

Cristina M Santana Maldonado, Dong-Suk Kim, Benton Purnell, Rui Li, Gordon F Buchanan, Jodi Smith, Daniel R Thedens, Phillip Gauger and Wilson K Rumbeiha
Toxicology (Amsterdam), Vol.485, 153424
01/04/2023
DOI: 10.1016/j.tox.2023.153424
PMID: 36610655
url
https://doi.org/10.1016/j.tox.2023.153424View
Published (Version of record) Open Access

Abstract

Hydrogen sulfide (H S) is a toxin affecting the cardiovascular, respiratory, and central nervous systems. Acute H S exposure is associated with a high rate of mortality and morbidity. The precise pathophysiology of H S-induced death is a controversial topic; however, inhibition of the respiratory center in the brainstem is commonly cited as a cause of death. There is a knowledge gap on toxicity and toxic mechanisms of acute H S poisoning on the brainstem, a brain region responsible for regulating many reflective and vital functions. Serotonin (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) play a role in maintaining a normal stable respiratory rhythmicity. We hypothesized that the inhibitory respiratory effects of H S poisoning are mediated by 5-HT in the respiratory center of the brainstem. Male C57BL/6 mice were exposed once to an LCt concentration of H S (1000 ppm). Batches of surviving mice were euthanized at 5min, 2h, 12h, 24h, 72h, and on day 7 post-exposure. Pulmonary function, vigilance state, and mortality were monitored during exposure. The brainstem was analyzed for DA, 3,4-dehydroxyphenyl acetic acid (DOPAC), 5-HT, 5-hydroxyindoleatic acid (5-HIAA), norepinephrine (NE), GABA, glutamate, and glycine using HPLC. Enzymatic activities of monoamine oxidases (MAO) were also measured in the brainstem using commercial kits. Neurodegeneration was assessed using immunohistochemistry and magnetic resonance imaging. Results showed that DA and DOPAC were significantly increased at 5min post H S exposure. However, by 2h DA returned to normal. Activities of MAO were significantly increased at 5min and 2h post-exposure. In contrast, NE was significantly decreased at 5min and 2h post-exposure. Glutamate was overly sensitive to H S-induced toxicity manifesting a time-dependent concentration reduction throughout the 7 day duration of the study. Remarkably, there were no changes in 5-HT, 5-HIAA, glycine, or GABA concentrations. Cytochrome c oxidase activity was inhibited but recovered by 24h. Neurodegeneration was observed starting at 72h post H S exposure in select brainstem regions. We conclude that acute H S exposure causes differential effects on brainstem neurotransmitters. H S also induces neurodegeneration and biochemical changes in the brainstem. Additional work is needed to fully understand the implications of both the short- and long-term effects of acute H S poisoning on vital functions regulated by the brainstem.
 Neurotransmitters Hydrogen sulfide neurodegeneration pulmonary function respiratory depression brainstem

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