Hydrogen Sulfide-releasing Compounds Attenuate Lipopolysaccharide-induced Inflammation in Porcine Anterior Uveal Explants, Ex Vivo
Year: 2026
Type: preprint
Abstract: In the present study, we investigated the pharmacological actions of both fast- and slow-releasing H 2 S compounds, as well as polysulfides, on acute inflammation induced by the bacterial lipopolysaccharide (LPS) in an ex vivo porcine model of anterior uveitis. Isolated porcine iris-ciliary bodies (ICB) were maintained in oxygenated Krebs-Henseleit solution and then incubated in separate wells of RPMI 1640 supplemented media with an antibiotic. ICBs were exposed to sodium hydrosulfide (NaHS), GYY4137, S-allyl-cysteine (SAC), and polysulfides, diallyl disulfide (DADS), and diallyl tetrasulfide (DATTS) four hours before the end of incubation. We observed that LPS (5–200 ng/ml) produced increases in the release of pro-inflammatory mediators (TNF-α, IL-6, and PGE 2 ) and a corresponding decrease in the anti-inflammatory marker, IL-10, in the ICB explants. Both fast- (NaHS, 0.001–100 µM) and slow-releasing H 2 S compounds (GYY4137, 0.001–10 µM) and the organosulfur H 2 S-releasing compounds, DADS (0.001–300 µM), SAC (0.1–1000 nM), and DATTS (0.001 pM − 1 µM), caused a concentration-dependent attenuation of LPS-induced increases in the levels of TNF-α, IL-6, and PGE 2 . DATTS (0.001 pM – 10 nM) reversed the LPS (25 ng/ml)-induced decrease in IL-10 production in the explants. We conclude that both fast- and slow-releasing H 2 S compounds, as well as polysulfides, were effective in reducing LPS-induced acute inflammation in porcine anterior uveal explants, ex vivo. Inhibition of endogenous H 2 S biosynthesis exacerbates LPS-induced production of an inflammatory mediator, a response that was reversed by an H 2 S-releasing compound.
Source: Research Square
Institutions: Texas Southern University, Creighton University
Language: English
Topic: Sulfur Compounds in Biology
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W7134164941