Hydrogen Sulfide Reduces Ischemia and Reperfusion Injury in Neuronal Cells in a Dose- and Time-Dependent Manner.

Background: The ischemia-reperfusion injury (IRI) of neuronal tissue, such as the brain and retina, leads to possible cell death and loss of function. Current treatment options are limited, but preliminary observations suggest a protective effect of hydrogen sulfide (HS). However, the dosage, timing, and mechanism of inhaled HS treatment after IRI requires further exploration.

Methods: We investigated possible neuroprotective effects of inhaled HS by inducing retinal ischemia-reperfusion injury in rats for the duration of 1 h (120 mmHg), followed by the administration of hydrogen sulfide (HS) for 1 h at different time points (0, 1.5, and 3 h after the initiation of reperfusion) and at different HS concentrations (120, 80, and 40 ppm). We quantified the HS effect by conducting retinal ganglion cell counts in fluorogold-labeled animals 7 days after IRI. The retinal tissue was harvested after 24 h for molecular analysis, including qPCR and Western blotting. Apoptotic and inflammatory mediators, transcription factors, and markers for oxidative stress were investigated. Histological analyses of the retina and the detection of inflammatory cytokines in serum assays were also performed.

Results: The effects of inhaled HS were most evident at a concentration of 80 ppm administered 1.5 h after IRI. HS treatment increased the expression of anti-apoptotic Bcl-2, decreased pro-apoptotic Bax expression, reduced the release of the inflammatory cytokines IL-1β and TNF-α, attenuated NF-κB p65, and enhanced Akt phosphorylation. HS also downregulated NOX4 and cystathionine β-synthase. Histological analyses illustrated a reduction in TNF-α in retinal ganglion cells and lower serum levels of TNF-α in HS-treated animals after IRI.

Conclusion: After neuronal IRI, HS mediates neuroprotection in a time- and dose-dependent manner. The HS treatment modulated transcription factor NF-κB activation and reduced retinal inflammation.